medwireNews: Semaglutide increases walking capacity and improves symptoms and quality of life versus placebo in people with type 2 diabetes and symptomatic peripheral artery disease, phase 3 study findings indicate.
“These benefits coupled with previously described benefits for reducing major adverse cardiovascular events in patients with peripheral artery disease support semaglutide as a novel therapy that improves both function and outcomes in people with diabetes and peripheral artery disease,” write Marc Bonaca (University of Colorado School of Medicine, Aurora, USA) and co- authors in The Lancet.
They explain that, at present, there are limited therapies available to improve functional capacity and health-related quality of life in people with lower limb peripheral artery disease. To address this, Bonaca and team investigated whether the glucagon-like peptide-1 receptor agonist semaglutide could fill the gap.
The STRIDE trial included 792 participants (median age 68 years, 75% men) with type 2 diabetes and peripheral artery disease with intermittent claudication (Fontaine stage IIa, able to walk >200 m on a flat treadmill) and an ankle–brachial index of 0.90 or lower, or a toe–brachial index of 0.70 or lower.
The patients, from 112 outpatient clinical trial sites in 20 countries in North America, Asia, and Europe, were randomly assigned to receive once-weekly subcutaneous semaglutide 1.0 mg (n=396) or placebo (n=396) for 52 weeks.
The researchers report that, at 52 weeks, the median maximum walking distance at a 12% incline increased by a significantly greater degree with semaglutide than with placebo when measured as a ratio relative to the baseline median of 185 m, at 1.12 vs 1.08.
In absolute terms, this meant that people given semaglutide could walk a median of 26.4 m further at week 52 than those given placebo. This improvement remained significant at 5 weeks after study medication was discontinued, and Bonaca et al comment that “[t]he magnitude of benefit was consistent with previous approved therapies such as cilostazol and naftidrofuryl, and met prespecified criteria for a clinically meaningful change.”
There were also statistically significant and clinically meaningful improvements in all confirmatory secondary endpoints at week 52, including pain-free walking distance and quality of life, as well as reductions in the risk for the composite exploratory endpoints of rescue therapy or all-cause death, and for rescue therapy, all-cause death, or major adverse limb events.
There were no unexpected safety signals; five (1%) participants in the semaglutide group and six participants (2%) in the placebo group experienced adverse events that were possibly or probably treatment related, most commonly serious gastrointestinal events (1 vs 1%).
Bonaca and co-authors conclude that their findings, which were also presented at the American College of Cardiology Annual meeting (ACC.25) in Chicago, Illinois, USA, “could support prescribing and prioritisation among other therapies resulting in improved outcomes for this patient group.”
In an accompanying comment, Joshua Beckman (University of Texas Southwestern Medical Center, Dallas, USA) and Mark Creager (Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA) say that the STRIDE results “are an encouraging step forwards in addressing the treatment of patients with peripheral artery disease.”
They add: “Moving forward, it will be important to establish whether semaglutide improves walking capacity in patients with peripheral artery disease but without diabetes, and also to evaluate its longer-term effects on major adverse limb events, such as progression to chronic limb threatening ischaemia and the need for revascularisation or amputation.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet 2025; doi:10.1016/S0140-6736(25)00509-4
Lancet 2025; doi:10.1016/S0140-6736(25)00574-4
ACC.25; Chicago, Illinois, USA: 29–31 March