Metformin and exercise are often co-prescribed in adults with prediabetes and type 2 diabetes mellitus (T2DM). 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 (FFA), 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), non-acute (multiple doses), and habitual metformin (prescribed) intake were included in the systematic review. Study quality and risk of bias were assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses conducted on lactate, glucose, insulin, and exercise capacity during acute and non-acute studies and effects are reported as standardized mean differences (SMD) 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 weeks. Acute studies were primarily in young, healthy males, while 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 co-prescribing metformin and exercise.
Grammer et al. (Fri,) studied this question.