Metformin is associated with higher lactate concentrations during exercise in adults with prediabetes and type 2 diabetes

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American journal of physiology. Endocrinology and metabolism Published June 7, 2026 Medically reviewed June 7, 2026 Study authors: Grammer Emily E, Stahl Macy E, Ortiz de Zevallos Joaquin, Paterson Craig, Weltman Arthur, Allen Jaso… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note that metformin is associated with higher lactate concentrations during exercise in adults with prediabetes and T2DM.

This meta-analysis synthesized data from 325 participants to evaluate the effects of metformin on exercise metabolism and capacity in adults with prediabetes and type 2 diabetes mellitus. The analysis included both acute studies involving young, healthy males and habitual studies involving older adults, predominantly female.

The primary finding indicates that metformin was associated with greater lactate concentrations during exercise (SMD = 0.98; 95% CI: 0.36, 1.60; p = 0.002). Secondary outcomes such as glucose, insulin, and free fatty acids were also assessed but specific pooled effect sizes for these metrics were not reported in the primary results.

While the data suggests a clear association between metformin use and increased lactate levels during exercise, the authors note that the direction of interactions may depend on dose, duration, and participant characteristics. No specific limitations regarding study quality or safety outcomes were reported in the provided data.

These findings provide clinical insight for physicians and exercise practitioners when managing patients with prediabetes or type 2 diabetes who are engaging in physical activity while taking metformin. The results suggest a measurable physiological response to metformin during exercise, though individual patient factors may influence the magnitude of this effect.

Study Details

Study typeMeta analysis

Sample sizen = 325

EvidenceLevel 1

PublishedJun 2026

PMID42139118

View Original Abstract ↓

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, = 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, = 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.