Exercise is supposed to help prevent diabetes, not lose its punch because of a drug meant to do the same thing. Yet new research from Rutgers University suggests that the popular diabetes medication metformin could be dulling the body’s most powerful natural defense against the disease: exercise.
In a 16-week clinical trial published in The Journal of Clinical Endocrinology & Metabolism, researchers found that metformin blunted key improvements in blood vessel function, aerobic fitness, and blood sugar regulation that usually follow a regular exercise program. The results challenge long-standing clinical advice to pair metformin with physical activity for maximum benefit.
When Two Good Treatments Collide
“Most health care providers assume one plus one equals two,” said Steven Malin, lead author and professor in Rutgers’ Department of Kinesiology and Health. “The problem is that most evidence shows metformin blunts exercise benefits.”
The study involved 72 adults at risk for metabolic syndrome, a cluster of conditions that raise the risk of diabetes and heart disease. Participants were randomly assigned to perform either high- or low-intensity exercise while taking either metformin or a placebo. Over the course of the trial, researchers tracked how well participants’ blood vessels responded to insulin, a sign of vascular health that also helps regulate blood sugar after meals.
Exercise alone improved this vascular insulin sensitivity, allowing blood to flow more efficiently and helping muscle tissues absorb glucose. But when metformin entered the mix, those improvements shrank. The drug also dampened gains in aerobic fitness and reduced positive changes in 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.”
For people who rely on both treatments, that finding is concerning. Exercise is expected to boost physical function and reduce blood sugar. If metformin undermines those effects, patients may not receive the full protection they expect.
A Cellular Tug-of-War
Why does metformin interfere with exercise gains? Malin’s team suspects the answer lies in how the drug works at the cellular level. Metformin helps lower blood sugar by partially blocking mitochondrial activity, reducing oxidative stress and improving insulin sensitivity. But those same mitochondria are responsible for adapting to exercise, building endurance, muscle, and cardiovascular health. In effect, the drug may be hindering the body’s ability to strengthen itself through training.
“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.”
Malin emphasized that the study should not discourage anyone from exercising or taking metformin. Instead, it highlights a need for better medical guidance on how to combine therapies safely and effectively. With nearly 35 million Americans living with type 2 diabetes, understanding how drugs and lifestyle interact could make or break prevention efforts.
The Journal of Clinical Endocrinology & Metabolism: 10.1210/clinem/dgaf551
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