Metformin May Diminish the Cardiometabolic Benefits of Exercise

Metformin use dulls crucial improvements in blood vessel function, fitness and blood sugar 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 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, patients were randomized to either low-intensity exercise plus placebo (∼55% VO₂max 5 day/week; LoEx + PL; n = 22) or metformin (2000 mg/d, LoEx + Met, n = 21); and high-intensity exercise plus PL (∼85% VO2max 5d/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 in aerobic fitness, as shown by increases in VO₂max (P < .05).^1,2

“Blood vessel function improved with exercise training, regardless of intensity,” Malin said. “Metformin blunted that observation, suggesting one type of exercise intensity is not better either 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-alpha (TNF-α), compared with the placebo groups (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 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 either with the drug for blood vessel health.”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 raises 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 its 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 S, Heiston E, Battillo D, et al. Metformin blunts vascular insulin sensitivity after exercise training in adults at risk for metabolic syndrome. The Journal of Clinical Endocrinology & Metabolism. 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. November 6, 2025. Accessed November 11, 2025. https://www.eurekalert.org/news-releases/1104961