GLP-1 RAs Linked to Lower Mortality, Amputation Risk in PAD and Type 2 Diabetes

July 6, 2026—Glucagon‐like peptide‐1 receptor agonists (GLP-1 RAs) were shown to be associated with lower risks of death, hospitalization, amputation, and lower-extremity revascularization compared with metformin among adults with type 2 diabetes and peripheral artery disease (PAD), according to the American Heart Association.

These findings from an observational analysis study were published by Akiva Rosenzveig, MD, et al in the Journal of the American Heart Association. Aravinda Nanjundappa, MD, the senior investigator of the study, and Dr. Rosenzveig are interventional cardiologists at the Cleveland Clinic in Cleveland, Ohio.

As summarized in the AHA press release, the investigators used the TriNetX global federated electronic health record database to identify adults aged ≥ 18 years with type 2 diabetes and PAD between January 2010 and January 2025.

After propensity matching, the primary analysis included 2,133 patients treated with GLP-1 RAs and 2,133 treated with metformin. The study included predominantly White patients (63%); 23% of patients identified as Black and 45% as women. Further details of the study are outlined in the AHA press release, which is available online here.

The investigators found that compared with metformin, GLP-1 RA therapy was associated with the following:

• A 26% reduction in all-cause mortality
• A 13% reduction in hospitalizations
• Up to a 48% reduction in amputations
• An approximately 36% reduction in revascularization procedures in obstructed lower extremity arteries

Rates of myocardial infarction, stroke, and serious kidney events were similar between the treatment groups.

The investigators also noted that the association between GLP-1 RA use and improved outcomes was strongest among patients with chronic limb-threatening ischemia and those with obesity (body mass index ≥ 30 kg/m²), reported the AHA press release.

“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 [PAD] has limited treatment options,” commented Dr. Nanjundappa in the AHA press release. “Our findings indicate these medications may improve long-term health for people with PAD, in addition to managing blood sugar and weight loss.”

Dr. Rosenzveig added, “Obesity and PAD, including chronic limb-threatening ischemia, are linked to increased inflammation, poor blood vessel function, insulin resistance, oxidative stress, and faster hardening of the arteries. These results indicate GLP1-RAs can help reduce inflammation, improve blood vessel function, and manage blood sugar levels.”

Investigators acknowledged that the retrospective observational design cannot establish causality and noted that reliance on electronic health records introduces the potential for diagnostic coding errors.

Joshua J. Joseph, MD, who is Chair of the Diabetes Committee for the AHA’s Council on Lifestyle and Cardiometabolic Health, discussed the study in the AHA press release.

“GLP1-RA medications may help people with PAD and type 2 diabetes live longer,” commented Dr. Joseph. “They might also help people reduce the risk of amputation and the number and length of hospitalizations. However, more research is needed to confirm these findings and understand the underlying mechanisms—is it due to reduced inflammation? It would also be important to know if GLP-1 RAs could be beneficial for people with PAD who do not have type 2 diabetes.”