Metformin May Diminish the Cardiometabolic Benefits of Exercise

Metformin use dulls crucial improvements in blood vessel function, fitness, and blood glucose control during exercise, according to data published in The Journal of Clinical Endocrinology & Metabolism. The findings provide clinicians and pharmacists with important considerations for counseling patients treated with metformin when engaging in physical activities.¹

Metformin is the first-line treatment for hyperglycemia and is often recommended for use during exercise. However, some studies show that it may interfere with the metabolic adaptations that occur during physical activity. This led researchers from Rutgers University to investigate whether metformin blunts vascular insulin sensitivity among adults at risk for metabolic syndrome.^1,2

They performed a double-blind, placebo-controlled trial in which patients were randomly assigned to either low-intensity exercise plus placebo (∼55% VO₂max 5 d/wk; LoEx + PL; n = 22) or metformin (2000 mg/d, LoEx + Met, n = 21); and high-intensity exercise plus PL (∼85% VO2max 5 d/wk, HiEx + PL, n = 24) or metformin (HiEx + Met, n = 24) for 16 weeks. To identify the impact of metformin, the researchers tracked changes in blood vessel function under insulin stimulation during the 16-week period.¹

Results showed that exercise without metformin was superior and that metformin reduced the overall metabolic benefits of physical activity. Exercise without metformin showed significant improvements in aerobic fitness, as shown by increases in VO₂max (P < .05).^1,2

“Blood vessel function improved with exercise training, regardless of intensity,” Steven Malin, a professor in the Department of Kinesiology and Health in the School of Arts and Sciences at Rutgers and the lead author of the study, said in a news release. “Metformin blunted that observation, suggesting one type of exercise intensity is not better than the other with the drug for blood vessel health.”²

Metformin reduced the positive vascular and metabolic effects typically seen with exercise. Specifically, it blunted the exercise-induced improvements in insulin-stimulated flow-mediated dilation and muscle blood flow, as well as the reductions in fasting glucose, endothelin-1, and tumor necrosis factor-α, compared with the placebo groups (P < .05).^1,2

Malin hypothesizes that metformin’s mechanism of action could be the underlying reason for decreased overall exercise benefit. Metformin blocks parts of the mitochondria, thereby reducing oxidative stress and improving insulin control. However, this mechanism may also interrupt the cellular adaptations triggered by exercise.²

The data raise critical questions for clinicians and pharmacists as they monitor patients treated with metformin. Exercise is a critical component of diabetes care, so ensuring patients are receiving the full benefits is necessary for optimal health outcomes.

“We need to figure out how to best recommend exercise with metformin,” Malin said. “We also need to consider how other medications interact with exercise to develop better guidelines for doctors to help people lower chronic disease risk.”²

REFERENCES

1. Malin SK, Heiston EM, Battillo DJ, et al. Metformin blunts vascular insulin sensitivity after exercise training in adults at risk for metabolic syndrome. J Clin Endocrinol Metab. Published online October 7, 2025. Accessed November 11, 2025. https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgaf551/8276136?redirectedFrom=fulltext

2. Why your daily walk might not work as well if you’re on metformin. News release. Rutgers University. November 6, 2025. Accessed November 11, 2025. https://www.eurekalert.org/news-releases/1104961