Many assume that combining exercise with the diabetes drug metformin delivers double the health benefits, but new research from Rutgers University challenges that assumption.<\/p>\n
In a 16-week trial, the study found that metformin actually reduced the improvements<\/a> in blood vessel function, fitness and blood sugar control that exercise normally provides.<\/p>\n Metformin and exercise<\/p>\n Type 2 diabetes affects ~35 million people in the United States<\/a>, and prevention strategies routinely emphasize a combination of lifestyle change and pharmacotherapy.<\/p>\n One major contributor to diabetes and heart disease is metabolic syndrome, a cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat and abnormal cholesterol.<\/p>\n Exercise is well known to improve vascular insulin sensitivity<\/a> (how blood vessels respond to insulin) and to boost aerobic fitness, both of which lower the risk of diabetes and cardiovascular disease. Enhancing vascular insulin sensitivity allows glucose to enter muscles more effectively, helping protect heart health.<\/p>\n In clinical practice, many healthcare providers operate on the assumption that prescribing exercise alongside the first-line drug metformin will deliver additive benefits \u2013 assuming that \u201cone plus one equals two,\u201d said lead author\u00a0Dr. Steven Malin<\/a>, a professor in the Department of Kinesiology and Health at Rutgers University.<\/p>\n According to emerging literature, that assumption may be flawed. <\/p>\n \u201cThe problem is that most evidence shows metformin blunts exercise benefits,\u201d Malin added.<\/p>\n Although both metformin and exercise independently improve glucose regulation, prior studies suggest that taking them together may not enhance exercise\u2019s effects<\/a>.<\/p>\n Until now, no large randomized controlled trial has tested whether metformin interferes with exercise-induced adaptations in vascular insulin sensitivity across different exercise intensities.<\/p>\n How metformin affects exercise benefits<\/p>\n Malin and the team designed a 16-week, double-blind, placebo-controlled trial to test how metformin might change the body\u2019s response to exercise. They recruited 72 sedentary adults who were at risk for metabolic syndrome, and participants were split into 4 groups: low-intensity exercise with a placebo, low-intensity exercise with metformin (2 g per day), high-intensity exercise with a placebo and high-intensity exercise with metformin. Each person trained five days a week, with three of the weekly sessions supervised to keep effort levels consistent.<\/p>\n The team focused on vascular insulin sensitivity, using advanced ultrasound imaging to track blood flow through large arteries and tiny capillaries. They also measured aerobic fitness (VO\u2082 max) and fasting glucose and inflammation markers such as endothelin-1 and TNF-\u03b1. These measures help track how exercise and metformin affect blood sugar control, inflammation and aerobic fitness, key indicators of metabolic and cardiovascular health.<\/p>\n Exercise alone led to clear improvements. Blood vessels became more responsive, blood sugar control improved and fitness levels rose, regardless of whether the exercise was gentle or hard.<\/p>\n However, when metformin was added, these gains were sharply reduced.<\/p>\n \u201cBlood vessel function improved with exercise training, regardless of intensity,\u201d said Malin. \u201cMetformin blunted that observation, suggesting one type of exercise intensity is not better either with the drug for blood vessel health.\u201d<\/p>\n Participants taking metformin also failed to gain fitness or show the usual drop in glucose. <\/p>\n \u201cIf you exercise and take metformin and your blood glucose does not go down, that\u2019s a problem,\u201d Malin said. <\/p>\n \u201cTheir physical function isn\u2019t getting better and that could have long-term health risks,\u201d he added.<\/p>\n Despite small reductions in weight across all groups, the data pointed to a consistent pattern: metformin appeared to dampen the body\u2019s normal response to exercise.<\/p>\n Why metformin may limit fitness and blood sugar gains<\/p>\n The results suggest metformin may work against some of the body\u2019s key benefits from exercise. The drug appeared to limit the improvements in blood vessel function, blood sugar control and aerobic fitness that normally follow training \u2013 raising questions about current diabetes prevention advice.<\/p>\n One explanation behind metformin’s action may lie in how it acts on the cell\u2019s energy machinery. The drug partly blocks mitochondrial complex I, a target that helps reduce oxidative stress and lower blood sugar. But those same mitochondria are what the body relies on to adapt to exercise. Limiting their activity could dampen the cellular changes that improve endurance and metabolic health.<\/p>\n The study also found signs that metformin may disrupt the balance between nitric oxide, which helps vessels relax, and endothelin-1, which causes them to tighten.<\/p>\n However, the authors acknowledge some limits. More than half of the imaging data were lost due to technical problems, and most participants were postmenopausal women, which narrows how far the results can be generalized. The study was also short-term and focused on arm blood vessels, even though participants exercised using their legs.<\/p>\n Despite these issues, the findings are consistent with earlier work.<\/p>\n Future studies should explore how to combine metformin and exercise safely and test these effects in larger, more diverse groups.<\/p>\n \u201cWe need to figure out how to best recommend exercise with metformin,\u201d said Malin. \u201cWe also need to consider how other medications interact with exercise to develop better guidelines for doctors to help people lower chronic disease risk.\u201d<\/p>\n \u00a0<\/p>\n Reference: 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. 2025:dgaf551. doi: 10.1210\/clinem\/dgaf551<\/a><\/p>\n \u00a0<\/p>\n