Influence of metformin on exercise metabolism and capacity: a systematic review and meta-analysis

Metformin and exercise are often coprescribed in adults with prediabetes and type 2 diabetes mellitus. However, metformin may alter metabolic responses to exercise. This systematic review and meta-analysis evaluated the impact of metformin on exercise metabolism, including lactate, glucose, insulin, and free fatty acids, along with exercise capacity. Electronic databases (Web of Science, PubMed/Medline, Embase, and SPORTDiscus) were searched through January 2025. Twenty-one studies that involved acute (single dose), nonacute (multiple doses), and habitual metformin (prescribed) intake were included in the systematic review. Study quality and risk of bias were assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were conducted on lactate, glucose, insulin, and exercise capacity during acute and nonacute studies, and effects are reported as standardized mean differences (SMDs) with 95% confidence intervals. Across 325 participants (female, n = 125), metformin doses ranged from 500 to 3,000 mg/day and interventions ranged from 1 dose to 12 wk. Acute studies were primarily in young, healthy males, whereas habitual studies involved older adults (predominantly female) on long-term metformin treatment. Metformin was associated with greater lactate concentrations during exercise (SMD = 0.98, 95% CI: 0.36, 1.60, P = 0.002). Metformin modulates exercise metabolism, with the largest impact being on lactate accumulation during exercise. The direction of these interactions may depend on dose, duration, and participant characteristics. This review provides the first critical synthesis of available literature combining metformin and exercise metabolism, capacity, and training adaptations, offering insights to clinicians and exercise practitioners on potential implications of coprescribing metformin and exercise.