Popular Diabetes Drug Metformin May Cancel Out Exercise Benefits, Study Warns

Rutgers researchers have discovered that a popular diabetes drug may reduce the health benefits people expect from it.

A commonly prescribed medication for diabetes might actually be working against one of the best-known ways to prevent the disease: exercise.

That finding comes from a Rutgers-led study published in The Journal of Clinical Endocrinology & Metabolism, which discovered that metformin reduces some of the key benefits normally gained from regular physical activity. These include improvements in blood vessel health, physical fitness, and the body’s ability to regulate blood sugar.

Since 2006, doctors have typically encouraged patients with elevated blood sugar levels to combine metformin with exercise, expecting that the two proven treatments would produce stronger results together. However, the new research suggests this may not be the case.

“Most health care providers assume one plus one equals two,” said 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. “The problem is that most evidence shows metformin blunts exercise benefits.”

Putting the Theory to the Test

To investigate the issue, Malin and his team studied 72 adults at risk for metabolic syndrome, a group of conditions known to increase the chances of developing diabetes and heart disease. Participants were split into four groups: high-intensity exercise with a placebo, high-intensity exercise with metformin, low-intensity exercise with a placebo, and low-intensity exercise with metformin.

For 16 weeks, the researchers monitored how blood vessels responded to insulin, a process that allows vessels to widen and deliver oxygen, hormones, and nutrients after eating.

The results were clear: Exercise alone improved vascular insulin sensitivity, meaning blood vessels responded better to insulin and allowed more blood flow to muscles. This matters because insulin’s ability to open blood vessels helps shuttle glucose out of the bloodstream and into tissues, lowering blood sugar after meals.

But when metformin was added, the improvements shrank. The drug also diminished gains in aerobic fitness and reduced the positive effects on inflammation and fasting glucose.

“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.”

This matters because exercise is supposed to lower blood sugar and improve physical function, crucial goals of diabetes treatment. If metformin interferes with those benefits, patients may not get the protection they expect to help lower disease risk.

Real-World Consequences

“If you exercise and take metformin and your blood glucose does not go down, that’s a problem,” Malin said. “People taking metformin also didn’t gain fitness. That means their physical function isn’t getting better and that could have long-term health risk.”

The implications go beyond lab measurements. Fitness gains translate into energy for daily life. This includes activities such as climbing stairs, playing with children, and staying active with friends. If those improvements stall, quality of life suffers, Malin said.

The findings don’t mean people should stop taking metformin or exercising, Malin said. Instead, it raises urgent questions for doctors about how the two treatments can be combined and the need for close monitoring. Malin hopes future research will uncover strategies that preserve the benefits of both.

Why does metformin blunt exercise benefits? The answer is unclear but may lie in the drug’s mechanism of action, Malin said. Metformin works partly by blocking parts of the mitochondria, which reduces oxidative stress and improves blood sugar control. But that same inhibition may interfere with the cellular adaptations triggered by exercise, including improvements in mitochondrial function and aerobic capacity. In other words, the very process that makes metformin effective may block the body’s ability to respond fully to physical training.

Previous research has hinted at similar effects, but this trial is among the first to examine vascular insulin sensitivity, which is a key factor controlling glucose regulation and cardiovascular health, Malin said. By showing that metformin can blunt improvements in both large arteries and tiny capillaries regardless of exercise intensity, the study underscores the complexity of combining such treatments.

The stakes are high, Malin said. Type 2 diabetes affects nearly 35 million people in the United States, and prevention strategies often hinge on lifestyle changes combined with medication. If those strategies don’t work as expected, patients could face greater risks down the road.

“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.”

Reference: “Metformin Blunts Vascular Insulin Sensitivity After Exercise Training in Adults at Risk for Metabolic Syndrome” by Steven K Malin, Emily M Heiston, Daniel J Battillo, Tristan J Ragland, Andrew J Gow, Sue A Shapses, Ankit M Shah, James T Patrie and Eugene J Barrett, 7 October 2025, The Journal of Clinical Endocrinology & Metabolism.
DOI: 10.1210/clinem/dgaf551

Funding: National Institutes of Health

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