Semaglutide Improves CV Function, Walk Distance in PAD | ACC 2025

The glucagon-like peptide 1 (GLP1) receptor agonist semaglutide significantly improved cardiovascular function and walking endurance, along with other quality-of-life measures, after one year in people with peripheral artery disease (PAD) and type 2 diabetes, according to results of a multinational phase 3b trial presented at the American College of Cardiology Scientific Session today in Chicago.

Marc Bonaca, M.D., M.P.H.

“GLP-1 receptor agonists (RAs) do a lot: cardiometabolic benefits, MACE (major adverse cardiovascular events) benefits, and so on,” lead author Marc Bonaca, M.D., M.P.H., director of vascular research at the University of Colorado School of Medicine in Aurora, said when presenting results of the STRIDE trial in a late breakers session at the meeting. The results were published simultaneously in the Lancet.

“For peripheral artery disease, we now know that semaglutide improves function, symptoms, hemodynamics and lowers the rate of progression to rescue,” he said. “And so we have overall a new drug for PAD.” The results also add some understanding to GLP-1s work, Bonaca said.

Semaglutide is sold by Novo Nordisk, a Danish company, as Ozempic for diabetes and as Wegovy for weight loss. Although it has an additional mechanism of action, tirzepatide is also grouped under the GLP-1 heading. Lilly sells tirzepatide as Mounjaro for diabetes and as Zepbound for weight loss. The positive STRIDE results add to an already large body of evidence suggesting that the GLP-1s produce an array of benefits across many disease categories.

The STRIDE trial enrolled 792 people with Type 2 diabetes and early-stage, symptomatic PAD. The researchers randomly assigned the participants to either weekly, 1-milligram subcutaneous injections of semaglutide or a placebo. The primary end point was change in maximum walking distance measured on the treadmill after 52 weeks of treatment.

The median body-mass index (BMI) in the study population was 28, which is lower than in other trials of semaglutide or GLP-1s, Bonaca noted, and about one-third of the participants had a BMI of less than 27. Still, the people were “severely disabled,” he said, and could only walk about one-tenth of a mile on the treadmill, he said.

After six months, a significant improvement in walking distance started to emerge in the semaglutide group compared with those in the placebo group, according to Bonaca. At the 52-week end point, the patients assigned to semaglutide improved their walking distance by an average of 87 meters compared to 41 meters for the placebo group.

“To put that into context, a change on a flat six-minute walk test that would be clinically meaningful for this population would be 20 meters,” Bonaca said, referencing a common measurement of walking used in medical research that measures how far a person can walk in six minutes. “This [result] is double that, and it’s on a 12% grade, so walking up a hill, which would be about a twofold increase in the metabolic equivalent of work, so it’s a large absolute delta.”

The effect was similar across all subgroups, Bonaca said.

The analysis included four secondary and exploratory outcomes: function, quality of life, hemodynamics, and a post hoc analysis of patients who needed rescue treatment, major adverse limb events, or mortality, all of which favored semaglutide over the placebo. With regard to the latter, 3.7% of the semaglutide group required rescue or had one of the outcomes compared with 8% of the placebo group.

The exploratory analyses are “one of the more exciting aspects, I would say,” said Eugenia Gianos, M.D., a cardiologist at Northwell Health in New York and chair of the American College of Cardiology Prevention of CVD Council, “but still to be taken with a grain of salt.”

The results are meaningful for preventive cardiologists, she said.

“We struggle to figure out how these very high-risk patients can get improvement in their outcomes,” Gianos added. “PAD patients are really suffering at the end of the day or dying from heart attack or stroke—heart conditions which they have shown in this exploratory analysis that they were able to substantially reduce up to 50% in combination cardiovascular outcomes and death.”

In the Lancet, Bonaca and his colleagues said the “research implications” of their results include a need for studies to further elucidate mechanisms of benefit of semaglutide and to assess the efficacy and safety in patients with PAD who do not have type 2 diabetes.

Novo Nordisk funded the study and the Lancet paper says the funder of the study was responsible for data collection, data analysis and trial conduct, and Bonaca and his co-authors were responsible for data interpretation

Bonaca is executive director of the Colorado Prevention Center, a nonprofit academic research organization affiliated with the University of Colorado that has received research grant or consulting funding from Novo Nordisk, among many other companies.