Most GLP-1 trials measure weight, blood sugar or heart events. STRIDE measured something blunter: how far people could actually walk before their legs made them stop.
Peripheral artery disease is atherosclerosis in the legs. Narrowed arteries starve the calf muscles of blood during exertion, and the result is intermittent claudication — a cramping ache that appears after a predictable distance and disappears with rest. The trial investigators put the global burden at more than 230 million people.
It is a quality-of-life disease as much as a vascular one. Someone whose walking limit is two hundred metres stops going to the shops, stops walking the dog, stops the exact activity that would help. And the drug options are thin: supervised exercise therapy, cilostazol, revascularisation for the worst cases. Very little else has ever moved the number.
That is the gap STRIDE was built to test.
STRIDE was a phase 3b, double-blind, placebo-controlled trial at 112 outpatient sites across 20 countries in North America, Europe and Asia, enrolling from October 2020 to July 2024. It randomised 792 people 1:1 to subcutaneous semaglutide 1.0 mg once weekly or placebo for 52 weeks.
Entry required both type 2 diabetes and symptomatic PAD: Fontaine stage IIa claudication, still able to walk more than 200 m, with an ankle-brachial index at or below 0.90 or a toe-brachial index at or below 0.70. Median age was 68; three quarters of participants were men.
The primary endpoint was deliberately physical rather than biochemical — maximum walking distance on a constant-load treadmill at week 52, expressed as a ratio to each person's own baseline. Participants were retested at week 26, week 52, and again at week 57, five weeks after the last injection.
The placebo group improved too — a ratio of 1.08 over a year, which is what repeated treadmill testing and trial-level attention tend to produce on their own. The semaglutide group improved more, and the gap between them was the result.
The effect was modest in absolute terms and consistent across every confirmatory secondary endpoint. Pain-free distance moved, patient-reported vascular quality of life moved, and the walking gain was still measurable five weeks after the last dose, though narrower.
Safety was unremarkable. Six serious adverse events in five semaglutide participants and nine in six placebo participants were judged possibly or probably treatment-related, mostly gastrointestinal. There were no treatment-related deaths.
Semaglutide 1.0 mg weekly increased maximum walking distance by an estimated 13% more than placebo over 52 weeks in people with type 2 diabetes and claudication — the first randomised evidence that a GLP-1 improves function, not just risk markers, in peripheral artery disease. STRIDE tested only people who also had type 2 diabetes, at the 1.0 mg diabetes dose, for one year.
Sources: Bonaca et al., The Lancet 2025;405:1580–1593 (STRIDE) · Lancet article page · ClinicalTrials.gov NCT04560998 · American College of Cardiology trial summary · Subgroup analysis, Diabetes Care 2025. Trial funded by Novo Nordisk.
The dose matters. STRIDE used semaglutide 1.0 mg — the Ozempic strength approved for type 2 diabetes — not the 2.4 mg weight-management dose. Nothing here says the higher dose does more for legs, or less.
The population matters more. Everyone in the trial had type 2 diabetes. Plenty of people with claudication do not, and the authors were explicit that extending the finding to them requires its own trial. PAD is also not an approved indication for semaglutide anywhere; this is one trial, not a label.
It is a function endpoint, not an event endpoint. Walking further is worth having on its own terms, but STRIDE was not sized to show fewer amputations or fewer revascularisations.
One practical note that generalises past PAD: the benefit sat on top of a full year of weekly dosing, and it had already started shrinking five weeks after the injections stopped. Weekly drugs only work weekly. GLP1ShotDay exists to keep that schedule from drifting — one shot day, one reminder, one log of what was taken and when.
This article summarizes published clinical trial results for general education. It is not medical advice and does not replace guidance from your prescriber. Semaglutide is not approved for the treatment of peripheral artery disease. Never start, stop, or adjust a prescription based on an article.