A new international study found that semaglutide, a once-weekly injection, improved walking ability in people with peripheral artery disease and type 2 diabetes, according to the results of a new international study.
The STRIDE trial, recently published in The Lancet, followed 792 adults across 20 countries over 52 weeks. All had PAD with intermittent claudication and type 2 diabetes. Patients were randomly given semaglutide or a placebo and were assessed on their walking performance using a treadmill with a 12% incline.
By week 52, patients in the semaglutide group had a 13% greater improvement in maximum walking distance compared to placebo. This translated to a median increase of 26.4 meters and a mean increase of 39.9 meters, both measured from baseline. These improvements persisted 5 weeks after treatment discontinuation, with a median ratio to baseline at week 57 of 1.16 for semaglutide versus 1.1 for placebo.
"There were statistically significant improvements in all confirmatory secondary endpoints, including pain-free walking distance (symptoms) and quality of life," said Marc P. Bonaca, MD, from CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, and colleagues. "The observed differences met the prespecified anchor criteria for clinically meaningful change."
Patients receiving semaglutide also reported less leg pain and better physical function. These outcomes were assessed using the Vascular Quality of Life Questionnaire-6 and the SF-36 physical functioning domain. The improvement in pain-free walking distance reached a median of 22 meters versus 12 meters with placebo. Additionally, ankle-brachial index showed statistically significant improvement with semaglutide (ratio to baseline: 1.06) compared to placebo (1.02), with an estimated treatment ratio of 1.05.
Additional clinical benefits included greater weight reduction (–5.2 kg with semaglutide versus –1.2 kg with placebo) and lower hemoglobin A1c (–1.0% versus +0.2%). Analysis showed only a weak relationship between BMI change and walking distance improvement in both groups, suggesting that weight loss alone did not account for the benefits.
Adverse events occurred in 53% of participants on semaglutide and 46% on placebo. Most events were mild to moderate and primarily gastrointestinal. Serious adverse events affected 19% and 20% of participants in the semaglutide and placebo groups, respectively. No treatment-related deaths were reported.
Fewer patients in the semaglutide group required rescue therapy—defined as revascularization or new medical treatment—compared with placebo (4% versus 8%). A composite endpoint analysis also showed a lower rate of all-cause mortality and rescue treatment with semaglutide.
Lower limb PAD affects more than 230 million individuals worldwide, limiting mobility and causing pain when walking. While supervised exercise therapy is recommended, it is often underutilized, and drug options are limited. Semaglutide, already approved for type 2 diabetes and obesity, may offer an additional benefit for functional impairment in PAD.
The trial was funded by Novo Nordisk and conducted with oversight by ethics committees and an independent safety board. The study was registered at ClinicalTrials.gov (NCT04560998).
Author disclosures are available in the original publication.