A new study published today in the Journal of the American Heart Association reveals that GLP-1 receptor agonist (GLP-1 RA) medications, commonly used to treat Type 2 diabetes and aid weight loss, may significantly improve outcomes for patients who also have peripheral artery disease (PAD). The research, which analyzed health records of over 2,000 adults, found that GLP-1 RAs reduced all-cause deaths by 26%, hospitalizations by 13%, and amputations by up to 48% compared to metformin, the standard diabetes medication.
Peripheral artery disease involves narrowing of arteries in the legs, often due to atherosclerosis. It affects about 12.5 million U.S. adults aged 40 and older, according to the American Heart Association’s 2026 statistics. The study, led by Dr. Aravinda Nanjundappa of the Cleveland Clinic, also noted a 36% reduction in the need for procedures to restore blood flow to the legs among GLP-1 RA users. However, rates of heart attack, stroke, and serious kidney events were similar between the GLP-1 RA and metformin groups.
“Because GLP-1 RAs show significant benefits, especially for high-risk patients with severe circulation problems in their legs, clinicians should consider prescribing GLP-1s because peripheral artery disease has limited treatment options,” said study author Aravinda Nanjundappa, M.D. The strongest benefits were observed in patients with chronic limb-threatening ischemia and those with obesity (BMI of 30 or higher).
Study coauthor Akiva Rosenzveig, M.D., a cardiology fellow at the Cleveland Clinic, explained that obesity and PAD are linked to increased inflammation and oxidative stress. “These results indicate GLP1-RAs can help reduce inflammation, improve blood vessel function and manage blood sugar levels.”
The research used the TriNetX database to identify patients from January 2010 through January 2025. After matching, 2,133 patients per group were analyzed. Limitations include the inability to prove cause and effect and potential coding errors in electronic health records.
Joshua J. Joseph, M.D., an American Heart Association volunteer expert, commented that the findings suggest GLP-1 RAs may help patients live longer and reduce amputation risk, but more research is needed to understand the underlying mechanisms and to explore benefits for PAD patients without Type 2 diabetes.
The study was published in the Journal of the American Heart Association, an open-access journal. More details can be found in the full manuscript available online. The American Heart Association receives funding from various sources, including corporations, but maintains strict policies to prevent influence on its science content.
