STRIDE shows semaglutide improves walking distance in peripheral artery disease

Novo Nordisk presented results from the STRIDE trial on March 29, 2025 at the American College of Cardiology Annual Scientific Session in Chicago, with simultaneous publication in The Lancet ^[1][3]. In adults with type 2 diabetes and symptomatic peripheral artery disease (PAD), once-weekly semaglutide 1 mg — the dose sold as Ozempic — improved maximum treadmill walking distance by 13% compared with placebo ^[3][6].

What the trial measured

STRIDE was a phase 3b, double-blind, randomized, placebo-controlled trial run at 112 outpatient sites in 20 countries across North America, Asia and Europe, enrolling from October 1, 2020 to July 12, 2024 ^[4]. Of 1,363 people screened, 792 were randomly assigned 1:1 to semaglutide 1 mg once weekly (n=396) or matching placebo (n=396) for 52 weeks, on top of standard care ^[3][4]. Median age was 68, and 195 participants (25%) were female ^[4]. Everyone had type 2 diabetes plus early-stage symptomatic PAD (Fontaine stage IIa) with an ankle-brachial index of 0.90 or lower, or a toe-brachial index of 0.70 or lower ^[4]. Baseline median maximum walking distance was 185 meters ^[2].

The primary endpoint was the ratio of maximum walking distance at week 52 versus baseline on a constant-load treadmill ^[4]. The semaglutide group's median walking distance rose to 1.21 times baseline versus 1.08 in the placebo group — an estimated treatment ratio of 1.13 (95% CI 1.06–1.21; p=0.0004) ^[4]. MedPage Today described that as a 21% improvement with semaglutide versus 8% with placebo ^[2]. In absolute terms, the median difference was 26.4 meters (95% CI 11.8–40.9), about 87 feet, measured on a 12% incline ^[3][6].

Secondary endpoints also favored semaglutide: pain-free walking distance at week 52 (estimated treatment ratio 1.11; 95% CI 1.03–1.20; p=0.0046) and the Vascular Quality of Life Questionnaire-6 score (1.00; 95% CI 0.48–1.52; p=0.011) ^[1][3]. The sources describe that quality-of-life figure differently — Novo Nordisk and Endocrinology Advisor call it an estimated treatment difference, while the ACC summary lists it among treatment ratios ^[1][3][6]. Walking benefit was still present five weeks after treatment ended, at week 57 (1.08; 95% CI 1.00–1.16; p=0.038) ^[1].

Safety and open questions

Serious adverse events occurred in 74 participants (19%) on semaglutide and 78 (20%) on placebo; those judged possibly or probably treatment-related were 5 (1%) and 6 (2%) ^[3]. Three deaths (1%) occurred in the semaglutide arm and eight (2%) in the placebo arm, none treatment-related ^[3][4]. Permanent discontinuation of study treatment was 14% versus 11% ^[2]. An exploratory analysis found fewer combined rescue-therapy events or deaths with semaglutide (4% vs 8%; HR 0.46, 95% CI 0.24–0.85), a finding the investigators say needs confirmation ^[2].

The trial did not include people with PAD who do not have type 2 diabetes, and limb-event rates were too low to analyze major adverse limb events ^[2][4]. Lead investigator Marc Bonaca of the University of Colorado School of Medicine said at an ACC press conference, "We haven't had a new therapy for function in PAD in 25 years" ^[2]. Commenting independently, Johns Hopkins cardiologist Chiadi Ndumele said "it seems clear that the benefits are not very weight dependent, suggesting that semaglutide has direct vascular benefits" ^[2].

Why it matters for patients

Roughly 12 million people in the United States have PAD, and about one in four of them also has type 2 diabetes ^[3]. PAD often causes leg pain while walking, and drug options for walking function are limited — the only guideline-recommended one is cilostazol, which has no proven cardiovascular benefit and is used infrequently because of side effects ^[2]. In STRIDE, 11% of participants were already taking cilostazol, about 80% metformin, 35% an SGLT2 inhibitor and 52% aspirin, so semaglutide was added on top of usual care ^[2].

The measured gain is real but modest in absolute terms: about 26 meters of extra treadmill distance at 52 weeks ^[3]. STRIDE tested Ozempic 1 mg, not the 2.4 mg obesity dose sold as Wegovy, and only in people who also had type 2 diabetes ^[3][4].

What happens next

Novo Nordisk submitted a label extension application for Ozempic to the FDA based on STRIDE, and the agency accepted it for review; a decision was anticipated in 2025 ^[3][6]. Whether the FDA acted, and what any new labeling says, is not stated in these sources.