{"publication_id":"d8f38608-04e9-4baf-a98a-b15cef29f955","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 43/56 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Liraglutide, a glucagon-like peptide-1 receptor agonist, is now evaluated across an unusually broad slate of cardiometabolic, renal, hepatic, neurologic, and behavioral biomarkers, with regulatory and clinical interest extending well beyond glycemic control (Teng 2024; Yeo 2025). Whether the surrogate-endpoint signals that drive most biomarker reports translate into clinically meaningful aging-related benefit remains unresolved, an issue framed by Ioannidis-style surrogate-endpoint caution (Ioannidis 2005). We applied an AI-assisted structured evidence synthesis with an explicit audit trail, restricting the analytic frame to direct human randomized or longitudinal evidence on liraglutide and separating it from mechanistic or cross-domain signals. We conclude that liraglutide produces reproducible within-class cardiometabolic biomarker gains in direct RCTs, while its purported broader aging-related biomarker benefits are not yet demonstrated and should be treated as hypothesis-generating until adequately powered direct trials report hard functional endpoints. **Evidence-abstraction note.","citation_support":[{"source_id":"source_1","study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","support_kind":"cited_as_match","cited_as":"Teng 2024","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82])."},{"source_id":"source_34","study":"Efficacy and safety of glucagon‐like peptide 1 receptor agonists across all health outcomes in type 2 diabetes: An umbrella review and evidence map of randomised controlled trials","doi":"10.1111/dom.70298","url":"https://doi.org/10.1111/dom.70298","support_kind":"cited_as_match","cited_as":"Yeo 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"AIM: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been established as effective treatments for type 2 diabetes, offering benefits beyond glycaemic control; however, their associations across multiple health outcomes remain insufficiently assessed. Thus, we conducted an umbrella review of meta-analyses of randomised controlled trials (RCTs) to comprehensively evaluate the broad spectrum of their effects. MATERIALS AND METHODS: We conducted a systematic search of PubMed/MEDLINE, Embase, CINAHL, and Google Scholar through June 13, 2025, to identify meta-analyses of RCTs assessing the effects of GLP-1RAs on various health outcomes, including cardiovascular, renal, metabolic, oncologic, gastrointestinal and other domains. Effect sizes were recalculated using random-effects models and converted to equivalent odds ratios (eORs) with 95% confidence intervals (CIs) for consistency. The methodological quality of each review was assessed using the AMSTAR 2, and the certainty of evidence for each association was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation framework (high, moderate, low or very low certainty)."}],"candidate_sources":[]},{"claim_id":"claim_2","claim":"Evidence-honesty note: 43/56 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"We applied an AI-assisted structured evidence synthesis with an explicit audit trail, restricting the analytic frame to direct human randomized or longitudinal evidence on liraglutide and separating it from mechanistic or cross-domain signals.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Evidence-abstraction note.** The 56 retained reference papers are not 56 independent primary clinical trials: 43 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 13 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"This synthesis evaluates evidence on liraglutide biomarker effects across 56 included source papers and 3841 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"The corpus contains 13 direct clinical sources, 42 adjacent, review, or context sources, and 1 mechanistic or model-system source. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"Additional corpus sources included animal/preclinical evidence; the background evidence for liraglutide biomarker effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Seino 2022, Hany 2023, Pandey 2024 are interpreted separately from mechanistic studies such as Long 2025, because these evidence roles answer different questions about aging biology and clinical translation.","citation_support":[{"source_id":"source_25","study":"Combination metformin and liraglutide in PCOS: clinical efficacy in women and preclinical insights from gut microbiome modulation in rats","doi":"10.3389/fendo.2025.1599879","url":"https://doi.org/10.3389/fendo.2025.1599879","support_kind":"cited_as_match","cited_as":"Long 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"mechanistic","excerpt":"BACKGROUND: Metformin and liraglutide have been gradually used in the treatment of polycystic ovary syndrome (PCOS) due to their metabolic benefits, but also with some adverse reactions. Evidence suggests that gut microbiota imbalance plays an important role in the pathogenesis of PCOS. This study comprised a clinical trial to evaluate the efficacy of metformin, liraglutide, and their combination in PCOS women, and a parallel animal experiment to explore the potential involvement of gut microbiota. METHODS: In an open-label randomized controlled trial, sixty overweight/obese women with PCOS were randomized to: the MET group received oral metformin (0.85 g twice daily; n=20), the LIRA group received subcutaneous liraglutide (1.2 mg once daily; n=20), and the COM group received both treatments (n=20) for 12 weeks. In a separate animal study, female Sprague-Dawley rats were divided into five groups: (1) PCOS model group (letrozole 1 mg/kg orally); (2) MET group (letrozole + metformin 200 mg/kg orally); (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously); (4) COM group (letrozole + metformin + liraglutide at above doses); and (5) healthy controls (no treatment)."}],"candidate_sources":[]},{"claim_id":"claim_16","claim":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the cardiometabolic and contextual adjacent evidence outcome classes; and negative or adverse signals around the cardiometabolic and contextual adjacent evidence outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, longevity, mechanism); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |","citation_support":[],"candidate_sources":[{"study":"Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis","year":2024,"doi":"10.1186/s12902-024-01805-z","url":"https://doi.org/10.1186/s12902-024-01805-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Teng 2024","excerpt":"OBJECTIVE: The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. METHODS: An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). RESULTS: Twenty-eight RCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"A randomized trial to investigate the efficacy and safety of once‐daily liraglutide 1.8 mg in Japanese adults with type 2 diabetes exhibiting an inadequate response to liraglutide 0.9 mg","year":2022,"doi":"10.1111/jdi.13789","url":"https://doi.org/10.1111/jdi.13789","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Seino 2022","excerpt":"AIMS/INTRODUCTION: The present trial compared the efficacy and safety of once-daily liraglutide 1.8 mg with liraglutide 0.9 mg in Japanese patients with type 2 diabetes to assess the incremental effects of liraglutide 1.8 mg in those who exhibited an inadequate response to 0.9 mg. MATERIALS AND METHODS: This 26-week randomized trial (NCT02505334) enrolled Japanese adults with type 2 diabetes across 47 sites in Japan. Participants with glycated hemoglobin (HbA 1c ) 7.5-10.0% were included and those on insulin treatment were excluded. Participants discontinued pre-trial oral antidiabetic drug and initiated liraglutide 0.9 mg for a 12-week run-in period, after which those with HbA 1c ≥7.0% (466) were randomized (1:1) to two treatment arms: continuing liraglutide 0.9 mg or dose escalation to 1.8 mg. The change from baseline in HbA 1c (primary endpoint) and treatment-emergent adverse events (secondary endpoint) were measured at the end of 26 weeks. RESULTS: After 26 weeks of treatment, liraglutide 1.8 mg was more effective compared with 0.9 mg in lowering HbA 1c levels, with an estimated treatment difference of -0.40% (95% confidence interval [CI] -0.55, -0.24; P < 0.0001).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Comprehensive analysis of real-world data on liraglutide treatment in patients with obesity: a multicenter national study","year":2025,"doi":"10.1186/s40001-025-02836-5","url":"https://doi.org/10.1186/s40001-025-02836-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hepsen 2025","excerpt":"BACKGROUND: The study aimed to evaluate real-world data on liraglutide by assessing its efficacy, associated side effects, adverse events, and impact on metabolic parameters within the context of a multicenter national study. METHODS: This retrospective observational study analyzed data from 1009 patients across 38 endocrinology units from Türkiye. Patients with a history of bariatric surgery, those who started orlistat concurrently with liraglutide, and one patient who developed pancreatitis on the 15th day of treatment were excluded from the analyses of weight and laboratory changes. RESULTS: At least one side effect was observed in 48% of the patients, with nausea and vomiting being the most common. The most frequent reason for discontinuing treatment was the cost of the medication (42.6%). The median duration of liraglutide use was 4 months (IQR; 3-6), and the median dose was 2.4 mg (IQR; 1.8-3). Among the entire cohort, 76.4% and 40.9% of patients achieved a 5% and 10% weight loss target, respectively. Significant reductions were observed in metabolic parameters during the treatment.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","year":2025,"doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Huang 2025","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Boosting weight loss after conversional Roux-en-Y Gastric Bypass with liraglutide and placebo use. A double-blind-randomized controlled trial","year":2023,"doi":"10.1097/JS9.0000000000000990","url":"https://doi.org/10.1097/JS9.0000000000000990","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hany 2023","excerpt":"BACKGROUND: Conversional bariatric surgery inherently has less weight loss (WL) compared to primary procedures. Adjunctive use of the GLP-1 analog, liraglutide with conversional Roux-en-Y Gastric Bypass (cRYGB) may maximize the WL benefits of surgery. MATERIAL AND METHODS: This single-center randomized double-blind placebo-controlled trial included 80 patients randomized into two groups; the liraglutide group (40 patients) who received daily injections of liraglutide, and the placebo group (40 patients) who received normal saline starting at 6 weeks from cRYGB and continued for 6 months. After discontinuing the drugs at 6 months and unblinding, the patient were followed up to 12 months. The endpoints were percentage of total weight loss (%TWL) and percentage of excess weight loss (%EWL), and changes in the metabolic biomarkers, and complications within 30 and 90 days according to the global outcome benchmark (GOB) stratification. RESULTS: In total, 38 patients in the liraglutide group and 31 in the placebo group completed the 24 weeks. Liraglutide group experienced better WL with a significantly higher mean %TWL at 1 month (10.27±1.39 vs. 8.41±2.08), at 6 weeks (12.65±1.77 vs. 10.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"| Cardiometabolic | Bonga 2026: Incretin Analogues for Weight Reduction in Non-Diabetic Obese: A Review of Liraglutide, Semaglutide, and Tirzepatide Beyond Glycemic Control | direction=null | directness=indirect | B2 | outcome=Cardiometabolic; direction=null | finding=1 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_53","study":"Incretin Analogues for Weight Reduction in Non-Diabetic Obese: A Review of Liraglutide, Semaglutide, and Tirzepatide Beyond Glycemic Control","doi":"10.5041/RMMJ.10565","url":"https://doi.org/10.5041/RMMJ.10565","support_kind":"cited_as_match","cited_as":"Bonga 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"Obesity is a complex, multifactorial disease that contributes to a broad range of cardiometabolic, reproductive, and psychological disorders. Representing a major global health challenge, obesity can be addressed by lifestyle modifications such as reduced calorie intake, physical activity, adequate sleep, and stress management to help achieve sustainable weight loss and improve metabolic health in the long term. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two naturally produced incretin hormones in the gastrointestinal tract. Incretin analogues were initially approved for type 2 diabetes mellitus but were later found to exhibit weight-reducing properties. Liraglutide, semaglutide, and tirzepatide are the three incretin analogues approved for obesity in non-diabetic patients. This narrative review presents detailed comparisons of the three approved incretin analogues for obesity, their cost-effectiveness, and trends in the clinical setting."}],"candidate_sources":[]},{"claim_id":"claim_26","claim":"| Cardiometabolic | Dhippayom 2026: GLP ‐1 receptor agonists for treating obesity without diabetes: A systematic review and meta‐analysis of economic evaluations | direction=null | directness=review | B2 | outcome=Cardiometabolic; direction=null | finding=45 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_31","study":"GLP ‐1 receptor agonists for treating obesity without diabetes: A systematic review and meta‐analysis of economic evaluations","doi":"10.1111/dom.70322","url":"https://doi.org/10.1111/dom.70322","support_kind":"cited_as_match","cited_as":"Dhippayom 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"AIM: To pool the incremental net benefits (INBs) of using glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treating obesity without diabetes. MATERIALS AND METHODS: PubMed, Embase, EconLit, CEA Registry, ProQuest Dissertation and Theses Global were searched from inception to April 2024. Cost-effectiveness studies were included if they reported economic outcomes of any GLP-1RAs in the treatment of obesity without diabetes for a minimum time horizon of 5 years. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Monetary units were converted to 2023 US dollars. INBs with 95% confidence interval (CI) were pooled using a random-effects model. Statistical heterogeneity between studies was assessed using the I 2 statistic. The outcome was INB, calculated by multiplying the willingness-to-pay threshold by the difference in effectiveness between two interventions, then subtracting the difference in costs, with a positive INB indicating cost-effectiveness. RESULTS: Of 634 studies identified, 9 from high-income countries (HICs) with 23 comparisons were included."}],"candidate_sources":[]},{"claim_id":"claim_27","claim":"| Cardiometabolic | Dong 2025: Long-term administration of liraglutide for weight management in pediatric patients under 18 years: evidence from 7 randomized controlled trials. | direction=positive | directness=direct | A1 | outcome=Cardiometabolic; direction=positive | finding=representative statistic P = 0.007; source-level statistic reported |","citation_support":[{"source_id":"source_44","study":"Long-term administration of liraglutide for weight management in pediatric patients under 18 years: evidence from 7 randomized controlled trials.","doi":"10.1038/s41390-025-04537-5","url":"https://doi.org/10.1038/s41390-025-04537-5","support_kind":"cited_as_match","cited_as":"Dong 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"BACKGROUND: Liraglutide, an analog of glucagon-like peptide-1, is prescribed for managing weight in obese people. This meta-analysis investigated whether liraglutide was suitable for younger children with obesity, and to evaluate the efficacy and safety of varying treatment durations and dosage regimens. METHODS: Randomized controlled trials published up to March 20, 2025 were retrieved from in PubMed, Embase, Scopus, Cochrane library, Web of Science, and Google Scholar. RESULTS: Seven trials involving 575 patients were included in the analysis. Liraglutide significantly decreased body mass index (BMI) (WMD: -0.57; P = 0.007), BMI z-score (WMD: -0.45; P < 0.00001), body weight (WMD: -0.31; P = 0.0004), HbA1c (WMD: -0.43; P = 0.004), fasting plasma glucose (WMD: -1.23; P = 0.003) and systolic blood pressure (WMD: -0.20; P = 0.03) compared with placebos in obese children and adolescents. Subgroup analyses found that children 6-12 years of age did not have a significantly different BMI z-score (z = 1.76; P = 0.08) and body weight (z = 1.75; P = 0.08) versus adolescents. Fifty-six weeks of liraglutide treatment (z = 4.60; P < 0."}],"candidate_sources":[]},{"claim_id":"claim_28","claim":"| Cardiometabolic | Fang 2026: Effect of liraglutide on depressive symptoms in overweight or obese patients with type 2 diabetes: protocol for a pilot randomized controlled trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=6 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_46","study":"Effect of liraglutide on depressive symptoms in overweight or obese patients with type 2 diabetes: protocol for a pilot randomized controlled trial","doi":"10.3389/fendo.2025.1629157","url":"https://doi.org/10.3389/fendo.2025.1629157","support_kind":"cited_as_match","cited_as":"Fang 2026","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"INTRODUCTION: Patients with concurrent obesity, type 2 diabetes, and depression experience high disease severity and prevalence. This triad of conditions compromises quality of life and treatment adherence, further exacerbating disease progression. Therapeutic strategies for such patients must address both glycemic control and psychological well-being. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), offers benefits beyond glucose-lowering and weight reduction, with emerging evidence suggesting it may also alleviate depressive symptoms. Therefore, liraglutide represents a promising intervention for managing depression in patients with obesity and diabetes. OBJECTIVES: This study aims to assess the therapeutic efficacy of liraglutide in overweight or obese patients with type 2 diabetes and comorbid depression, with a specific focus on its antidepressant effects. METHODS: This is a randomized, double-blind, placebo-controlled pilot trial. Sixty eligible participants will be randomly assigned (1:1) to receive either liraglutide (initiated at 0.6 mg/day, titrated weekly to a maximum of 1.8 mg/day) or a matched placebo, as an adjunct to standard care for 12 weeks."}],"candidate_sources":[]},{"claim_id":"claim_29","claim":"| Cardiometabolic | Huang 2025: The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis | direction=unclear | directness=review | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative non-significant statistic P = 0.41; not treated as positive or negative directional support unless source direction is coded |","citation_support":[{"source_id":"source_4","study":"The safety and efficacy of liraglutide combined with metformin in clinical treatment of polycystic ovary syndrome patients: a meta-analysis","doi":"10.1186/s12905-025-03787-z","url":"https://doi.org/10.1186/s12905-025-03787-z","support_kind":"cited_as_match","cited_as":"Huang 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"OBJECTIVE: This study aims to investigate the effectiveness and safety of the combination of liraglutide and metformin for clinical treatment of patients with polycystic ovary syndrome. METHODS: Computerized searches were performed on PubMed, Embase, Web of Science, The Cochrane Library, CNKI, CBM, Wanfang, and VIP databases to collect randomized controlled trials(RCT) on the efficacy of metformin and liraglutide in the treatment of polycystic ovary syndrome. The search period spanned from the inception of the databases to August 2024. Following literature screening, data extraction, and risk of bias assessment in the included studies, two reviewers independently conducted meta-analysis using RevMan 5.4 software. RESULTS: A total of 12 RCT involving 1096 patients were analyzed. The meta-analysis revealed that the group receiving metformin combined with liraglutide demonstrated superiority over the group receiving metformin alone in terms of body mass index (BMI), glucose levels, lipid levels, hormone levels, establishment of menstrual cycles, normal ovulation rate, and rate of spontaneous conception."}],"candidate_sources":[]},{"claim_id":"claim_30","claim":"| Cardiometabolic | Lu 2026b: Efficacy of liraglutide on metabolic and reproductive outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis. | direction=null | directness=review | B1 | outcome=Cardiometabolic; direction=null | finding=1 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_54","study":"Efficacy of liraglutide on metabolic and reproductive outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis.","doi":"10.1111/dom.70452","url":"https://doi.org/10.1111/dom.70452","support_kind":"cited_as_match","cited_as":"Lu 2026b","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"Overweight or obese women with polycystic ovary syndrome (PCOS) frequently exhibit metabolic disturbances and reproductive dysfunction. This systematic review and meta-analysis evaluated the efficacy and safety of liraglutide in improving metabolic and reproductive outcomes in this population. PubMed, Embase, the Cochrane Library, Scopus, Web of Science and ClinicalTrials.gov were systematically searched from inception to 31 May 2025 for randomized controlled trials (RCTs) comparing liraglutide (alone or in combination) with placebo, metformin or non-liraglutide active treatments in overweight or obese women with PCOS. Two reviewers independently conducted study selection, data extraction and risk-of-bias assessment. Pooled analyses were performed using a random-effects model, and results were expressed as Hedges' g or odds ratios (ORs) with 95% confidence intervals (CIs). Seven RCTs comprising 330 women with PCOS were included. Compared with control treatments, liraglutide significantly increased menstrual frequency (g = 1.76; 95% CI [0.28, 3.24]), reduced body mass index (BMI; g = -0.52; [-0.94, -0."}],"candidate_sources":[]}]}