The effects of metformin and exercise training on cardiorespiratory, blood pressure, and metabolic adaptations across the spectrum of glucose dysregulation: a systematic review and meta-analysis
Abstract
Background: Metformin and structured exercise are routinely co-prescribed across the spectrum of glucose dysregulation, under the assumption of a cardiometabolic potentiating effect. Experimental data, however, suggest that metformin might blunt some exercise-induced adaptations, but this potential interaction has not been systematically quantified.
Methods: We conducted a systematic review and meta-analysis of controlled trials in adults with conditions across the spectrum of glucose dysregulation, comparing exercise plus metformin with the same exercise programme plus placebo or no metformin, including studies published between 1 January 2000 and 12 December 2025. Randomised and non-randomised controlled trials were eligible. Outcomes included peak oxygen uptake (VO2peak), body composition, blood pressure, glycaemic markers, and lipids. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models, and the certainty of evidence was assessed with GRADE. Heterogeneity was evaluated through Cochran's Q test and Higgins' I2 statistic, while publication bias was estimated based on the visual examination of the funnel plot, Egger's test, and selection models. This systematic review with meta-analysis was registered in PROSPERO (CRD420251167325).
Findings: Nine studies (n = 827; 14 publications) met the inclusion criteria; all contributed to the meta-analyses. Compared with exercise alone, metformin was associated with smaller improvements in…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 827 participants or records.
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