A new international study has found that semaglutide, a medication commonly used to treat type 2 diabetes and obesity, significantly improves walking distance, symptoms, and quality of life in people with peripheral artery disease (PAD) and type 2 diabetes.
The trial, called STRIDE, is the first to test the use of a GLP-1 agonist for managing PAD and has been published in The Lancet.
PAD affects over 200 million people worldwide, including 12 million in the U.S. It occurs when fat and cholesterol build up in the arteries of the legs, reducing blood flow and making it painful or difficult to walk.
PAD can also lead to dangerous complications, including non-healing wounds, limb amputation, and death. Yet, treatment options are limited. The only approved drug for improving walking ability in PAD, cilostazol, has significant side effects and is not safe for people with heart failure, making it rarely used.
In the STRIDE trial, 792 adults with type 2 diabetes and early-stage symptomatic PAD were randomly assigned to receive semaglutide (1 mg weekly) or a placebo for 52 weeks. The participants were from 112 medical centers across 20 countries. Their average age was 67, about a quarter were women, and two-thirds were white.
Researchers measured participants’ maximal walking distance on a treadmill at several points: at the start, after 26 weeks, after 52 weeks (the main assessment point), and again five weeks after stopping treatment.
At the beginning of the study, most patients were already quite impaired—they could only walk around 186 meters (roughly 0.1 miles) before symptoms like leg pain began.
By the end of the study, patients taking semaglutide had a median increase of 26 meters and an average improvement of 40 meters in how far they could walk—about a 13% improvement. While this may not sound like a lot, it’s considered meaningful in the context of PAD, where even a 10- to 20-meter increase is seen as clinically important.
Improvements extended beyond walking distance. Patients taking semaglutide reported better quality of life, including less leg pain and more ability to walk without discomfort. These improvements lasted even five weeks after stopping the drug. They also showed increased blood flow in the legs, as measured by the ankle brachial index—a key test for PAD.
Additionally, a post-hoc analysis showed that patients on semaglutide were 54% less likely to need urgent treatment for worsening symptoms (like artery-opening procedures) or to die from related complications. Only 14 patients in the semaglutide group needed such interventions compared to 30 in the placebo group.
Lead researcher Dr. Marc Bonaca from the University of Colorado School of Medicine emphasized the significance of these findings.
“This is the first new option in decades that not only improves walking ability, but also symptoms, blood flow, and overall quality of life for people with PAD and diabetes,” he said. “It may also help reduce the need for future invasive procedures.”
One key takeaway is that the benefits of semaglutide in PAD seem to go beyond weight loss, which was modest in this study. The results hint at a possible direct effect on blood vessels, suggesting semaglutide may improve circulation independently of its weight-related effects.
This raises hope that the drug could potentially help people with PAD who do not have type 2 diabetes—a possibility researchers hope to explore in future trials.
The trial had some limitations. All participants had type 2 diabetes, so the findings can’t yet be applied to people with PAD who don’t. Also, the study population was not fully diverse—only 14% were enrolled in North America, and there were relatively few Black participants, which may limit how broadly the results apply.
Despite these limitations, the STRIDE trial represents a major step forward in the treatment of PAD. For the millions of people struggling with reduced mobility, pain, and the risk of serious complications, semaglutide may offer a new path to better health and a better life.
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