STRIDE: Semaglutide and PAD Walking

STRIDE gives vascular clinicians a new reason to discuss semaglutide with a specific group of patients: adults who have type 2 diabetes and symptomatic peripheral artery disease (PAD), meaning narrowed leg arteries that cause pain during walking. In the 52-week trial, the median maximum walking-distance ratio was 1.21 with semaglutide and 1.08 with placebo. The estimated treatment ratio was 1.13 (95% confidence interval 1.06 to 1.21; p=0.0004)^[1]. That is evidence of a functional benefit in the population studied, not proof that semaglutide treats every form of PAD.

What STRIDE tested

STRIDE was a phase 3b, double-blind, randomised, placebo-controlled trial. Investigators enrolled 792 adults with type 2 diabetes and early symptomatic PAD with intermittent claudication, the exertional leg discomfort caused by reduced blood flow. Participants also had an ankle-brachial index of 0.90 or lower or a toe-brachial index of 0.70 or lower. These tests compare blood pressure in the limb with pressure in the arm. The trial assigned 396 people to semaglutide and 396 to placebo, both alongside usual care^[1].

The trial administered once-weekly subcutaneous semaglutide for 52 weeks, increasing from 0.25 mg to 0.5 mg and then 1.0 mg. The primary endpoint was change in maximum walking distance on a fixed treadmill test. Participants walked at 3.2 km/h on a 12% incline and continued after pain began until pain stopped further activity. The registered study also measured pain-free walking distance, PAD-specific quality of life, blood glucose, weight, blood pressure and vascular indices^[2]. These were trial procedures, not dosing instructions for clinical use.

The walking result

At week 52, the median ratio to baseline for maximum walking distance was 1.21 in the semaglutide group and 1.08 in the placebo group. Put plainly, both groups improved, but the semaglutide group improved more. The advantage was still present at the five-week follow-up after treatment ended: the registered results report ratios of 1.16 and 1.10, with an estimated treatment ratio of 1.08 (95% confidence interval 1.004 to 1.156; p=0.0380)^[2].

The secondary outcomes point in the same direction. At week 52, the median pain-free walking-distance ratio was 1.21 with semaglutide and 1.10 with placebo. The PAD-specific VascuQoL-6 score improved by a median 2 points with semaglutide and 1 point with placebo^[2]. The Lancet report concluded that semaglutide increased walking distance in people with symptomatic PAD and type 2 diabetes^[1].

The registry also reports mean changes in glycated haemoglobin, a measure of average blood glucose, of minus 0.8 percentage points with semaglutide and plus 0.2 points with placebo. Mean body-weight changes were minus 5.2 kg and minus 1.2 kg, respectively^[2]. Those differences provide metabolic context, but they do not show whether weight loss, glucose control, another pathway, or a combination caused the walking improvement.

What changes in vascular practice

The practical change is narrower than a new PAD treatment pathway. STRIDE supports considering functional status when vascular and diabetes teams review an eligible patient's glucose-lowering treatment. Walking limitation is often the symptom patients notice most, and the trial measured it directly rather than treating a laboratory marker as a substitute. A July 2026 editorial in the European Journal of Vascular and Endovascular Surgery focused specifically on STRIDE's implications for clinical vascular practice^[3].

The result does not displace supervised exercise, smoking cessation, antithrombotic and lipid-lowering therapy, foot care, or revascularisation when those are indicated. It also does not turn a treadmill gain into proof of fewer amputations, acute limb ischaemia events, heart attacks or deaths. STRIDE's primary question was walking capacity over 52 weeks^[1]. Vascular clinicians still have to treat the whole atherosclerotic disease, not one endpoint.

Safety and treatment boundaries

Serious adverse events judged possibly or probably related to treatment were reported in 5 of 396 participants assigned semaglutide and 6 of 395 who received placebo. Serious gastrointestinal events were the most frequent treatment-related serious events, and the investigators reported no treatment-related deaths^[1]. The US Ozempic label lists common gastrointestinal adverse reactions and warnings that clinicians must weigh against expected benefit for an individual patient^[4].

Anyone considering semaglutide should discuss the decision with a qualified healthcare professional who can review current medicines, diabetes control, eye disease, gastrointestinal history and other relevant risks. Our semaglutide regulation summary explains why authorised semaglutide products remain prescription medicines. STRIDE should inform a clinical conversation. It should not be used as a self-treatment protocol.

What we do not know yet

STRIDE enrolled people with type 2 diabetes, stable early symptomatic PAD and the ability to walk more than 200 metres before stopping. It excluded people whose walking was limited by several other conditions and those with a recent revascularisation procedure or a planned procedure^[2]. The findings therefore cannot be assumed to apply to PAD without diabetes, chronic limb-threatening ischaemia, active ulcers, recent intervention, or severe mobility limits.

The trial was funded by Novo Nordisk, the manufacturer of semaglutide^[1]. Its registry record reports 129 sites in 21 countries, while the peer-reviewed paper reports 112 outpatient sites in 20 countries. The reason for that difference is not clear from the records, but it does not change the randomised group sizes or the primary result. Future trials need to test people without diabetes and determine whether functional improvement is accompanied by fewer major limb events. For now, STRIDE supports a defined benefit in walking capacity for a defined patient group.