{"publication_id":"19dc964c-c04b-4c23-b723-e0397e5be483","content_hash":"sha256:aab877b0e1a9ba04878f2ca4ea27f8931192b29148f864b0962f1d5744991ce1","nodes":[{"id":"19dc964c-c04b-4c23-b723-e0397e5be483","type":"publication","title":"Alpha memo: metformin resistance training"},{"id":"claim_1","type":"claim","text":"Why this is surprising:** Receipt 1 establishes that metformin can interfere with resistance-training biology at the transcriptomic and hypertrophic level, yet Receipt 2 suggests the downstream glycaemic response to aerobic training survives metformin exposure — the same drug–exercise interaction thus appears molecularly disruptive but metabolically bounded."},{"id":"source_1","type":"source","study":"Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults","year":2020,"doi":"10.18632/aging.104096","url":"https://doi.org/10.18632/aging.104096","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":"primary","excerpt":"Evidence from clinical trials and observational studies suggests that both progressive resistance exercise training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response. To understand potential mechanisms underlying the inhibitory effect of metformin on PRT, we analyzed the muscle transcriptome in 23 metPRT and 24 plaPRT participants. PRT significantly increased expression of genes involved in extracellular matrix remodeling pathways, and downregulated RNA processing pathways in both groups, however, metformin attenuated the number of differentially expressed genes within these pathways compared to plaPRT. Pathway analysis showed that genes unique to metPRT modulated aging-relevant pathways, such as cellular senescence and autophagy. Differentially expressed genes from baseline biopsies in older adults compared to resting muscle from young volunteers were reduced following PRT in plaPRT and were further reduced in metPRT. We suggest that although metformin may blunt pathways induced by PRT to promote muscle hypertrophy, adjunctive metformin during PRT may have beneficial effects on aging-associated pathways in muscle from older adults."},{"id":"source_2","type":"source","study":"Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both?","year":2013,"doi":"10.1007/s00125-013-3026-6","url":"https://doi.org/10.1007/s00125-013-3026-6","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":"primary","excerpt":"Some previous studies suggested that metformin might attenuate the effects of exercise on glycaemia or fitness. We therefore examined whether metformin use influenced changes in glycaemic control, fitness, body weight or waist circumference resulting from aerobic and/or resistance training in people with type 2 diabetes participating in an exercise intervention trial. After a 4 week run-in period, participants from the Diabetes Aerobic and Resistance Exercise (DARE) trial were randomly assigned to 22 weeks of aerobic training alone, resistance training alone, combined aerobic and resistance exercise training or a waiting-list control group. Of the 251 randomised, 143 participants reported using metformin throughout the entire study period and 82 reported not using metformin at all. Compared with control, aerobic training led to a significant reduction in HbA1c in the metformin users (-0.57%, 95% CI -1.05, -0.10; -6.3 mmol/mol, 95% CI -11.5, -1.1) but not in the non-metformin users (-0.17, 95% CI -0.78, 0.43; -1.9 mmol/mol, 95% CI -8.5, 4.7). However, there were no significant differences in the changes in HbA1c (or fasting glucose) between metformin users and non-users in any of the exercise groups compared with control (p> 0.32 for all metformin by group by time interactions). Similarly, metformin did not affect changes in indicators of aerobic fitness, strength and body weight or waist circumference (p ≥ 0.15 for all metformin by group by time interactions). Contrary to our hypothesis and to previous short-term studies, metformin did not significantly attenuate the benefits of exercise on glycaemic control or fitness."}],"edges":[{"from":"19dc964c-c04b-4c23-b723-e0397e5be483","to":"claim_1","type":"contains_claim"}],"screening":{"identified":2,"screened":2,"excluded":0,"included":2,"included_or_retained":2,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"2 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}