Semaglutide Boosts PAD Outcomes in STRIDE with Marc P. Bonaca, MD, MPH

Results from the Phase 3b STRIDE trial suggest semaglutide 1.0 mg (Ozempic) could be the first therapy in nearly two decades to gain regulatory approval for improving functional outcomes in peripheral artery disease (PAD).

Presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, semaglutide benefited walking distance, quality of life, and ankle-brachial index in patients with PAD and type 2 diabetes (T2D). With currently limited PAD treatment options, the only guideline-recommended drug for symptoms is rarely used due to contraindications and side effects. As PAD progresses, patients often require revascularization procedures and face an increased risk of cardiovascular and limb events.

“I think we're seeing now that GLP-1 agonists are vascular drugs, and they do things that other drugs haven't done before,” study investigator Marc Bonaca, MD, MPH, a cardiologist and vascular medicine specialist serving as executive director of CPC and director of vascular research and professor of medicine at the University of Colorado Anschutz, told HCPLive. “This is a paradigm shift for PAD, but it also teaches us more about this class of agents and other things we may think about in the future.”

The Novo Nordisk-funded STRIDE trial enrolled 792 patients across 20 countries, randomizing them 1:1 to semaglutide or placebo for 52 weeks. At the study’s conclusion, semaglutide recipients experienced significantly greater improvements in maximum walking distance compared with placebo (estimated treatment ratio [ETR], 1.13; 95% CI, 1.06–1.21; P=.0004).

Additional analysis showed improvements in median maximum walking distance (ETR, 1.08; 95% CI, 1.00 to 1.16; P = 0.038), pain-free walking distance (ETR, 1.11; 95% CI, 1.03–1.20; P=.0046), and quality-of-life scores (ETR, 1.00; 95% CI, 0.48–1.52; P =.011).

Safety analysis found serious treatment-related adverse events in 1% of the semaglutide group and 2% of the placebo group, with gastrointestinal issues being the most common. No treatment-related deaths were reported.

Semaglutide’s benefits in PAD could be due to a direct vascular effect rather than weight loss, as the study population had a median BMI of 28.6 and a weak correlation between weight loss and outcomes. Future studies may explore whether patients with PAD but without type 2 diabetes could also benefit from semaglutide.

“I think what we found in STRIDE, in terms of significant improvement in every one of the pre-specified secondary endpoints, and the evidence of a direct vascular effect and benefit in the absence of weight loss, really suggests that this is a drug that should work for people who don't have diabetes,” Bonaca told HCPLive. “This needs to be tested in patients with PAD, regardless of diabetes status, similar to what was done in the SELECT trial for outcomes.”

Bonaca reports relevant disclosures with Abbott, Amgen, BMS, Merck, NovoNordisk, Sanofi, and others.

References

Campbell P. STRIDE: SEMAGLUTIDE improves functional outcomes in peripheral artery disease. HCP Live. March 29, 2025. Accessed April 3, 2025. https://www.hcplive.com/view/semaglutide-improves-functional-outcomes-in-peripheral-artery-disease.