Diabetes Medication Proves Ineffective for Peripheral Artery Disease Patients

A common diabetes medication does not help people with peripheral artery disease (PAD) and without diabetes walk farther, according to results from a major U.S. clinical trial published in JAMA. Peripheral artery disease (PAD) is a serious condition that affects blood flow to the legs, making walking painful and difficult. It impacts approximately 12 million adults in the U.S. and is linked to higher risks of heart attack and stroke. Despite its prevalence, few treatments effectively improve walking performance in these patients, said Mary McDermott, MD, ’92 GME, the Jeremiah Stamler Professor of Medicine in the Division of General Internal Medicine, who was first author of the study. “Walking exercise is first-line therapy, but walking exercise is difficult because people get ischemic pain when they walk for exercise,” said McDermott, who is also a professor of Preventive Medicine in the Division of Epidemiology. “There is one FDA-approved medication, but it’s not very effective and it’s associated with side effects.” In the study, investigators tested whether metformin — a widely used, inexpensive drug for type 2 diabetes — could help. Metformin has been shown to improve blood vessel health and reduce oxidative stress, leading scientists to believe it might also benefit PAD patients, even if they don’t have diabetes. The study, conducted at four U.S. medical centers, enrolled 202 adults with PAD. Participants were randomly assigned to take either metformin or a placebo for six months. The primary outcome was the change in distance walked during a six-minute test, a standard way to assess mobility. The results were clear: metformin did not make a difference. Both groups walked a shorter distance after six months, and the difference between metformin and placebo was negligible — just about one meter. Moving forward, McDermott and her collaborators will continue to search for effective treatments for PAD to ease the mobility difficulties patients experience, she said. “Based on the results of this clinical trial, we do not intend to continue studying metformin for peripheral artery disease,” McDermott said. “However, we have some preliminary evidence that cocoa flavanols and nicotinamide riboside both improved walking difficulty in peripheral artery disease, and we have some ongoing work that we expect will definitively establish the effects of those treatments.” The study was supported with funding from the National Heart Blood and Lung Institute (NHLBI) and Northwestern University. Reference: McDermott MM, Domanchuk KJ, Tian L, et al. Metformin to improve walking performance in lower extremity peripheral artery disease: the PERMET randomized clinical trial. JAMA. 2025. doi: 10.1001/jama.2025.21358