Leg Pain When You Walk? Semaglutide, the STRIDE Trial, and PAD in Men

In the STRIDE trial, weekly semaglutide 1 mg (the Ozempic dose) helped people with type 2 diabetes and early peripheral artery disease walk about 13% farther before leg pain stopped them, roughly 40 meters more than placebo after a year. EU regulators recommended adding the results to Ozempic's European label in 2025. As of October 2026, the US Ozempic label (revised May 2026) has no PAD indication and does not describe STRIDE, so in the US this remains trial evidence your doctor can weigh, not an approved use.

What PAD is, and why it sneaks up on men

Peripheral artery disease is plaque narrowing the arteries to your legs. The classic symptom is muscle pain or weakness in the calves, thighs, or buttocks that starts with walking and goes away within minutes of rest. Doctors call that claudication. More than 8 million Americans aged 40 and older have PAD, and only about 1 in 4 of them have symptoms, according to the National Heart, Lung, and Blood Institute.

The NHLBI's risk-factor page lists smoking, diabetes, high blood pressure, high cholesterol, chronic kidney disease, and age (most US patients are 65 or older). It also says men and women have similar overall risk, though women more often have no symptoms. So PAD isn't a "men's disease." But men with the classic risk stack (a smoking history, diabetes, high blood pressure) are exactly who shows up in PAD trials. Three-quarters of STRIDE's participants were men.

PAD matters beyond your legs. The NHLBI notes that plaque in the leg arteries can signal plaque in the heart and brain arteries, raising heart attack and stroke risk.

How STRIDE was designed

STRIDE was a phase 3b, double-blind, placebo-controlled trial run by Novo Nordisk at 112 sites in 20 countries. Results were presented at the American College of Cardiology meeting on March 29, 2025, and published the same day in The Lancet (Bonaca MP, et al.), according to the ACC's trial summary.

Source: ACC: STRIDE trial summary.

The trial excluded people with other conditions that limit walking, recent or planned leg revascularization, advanced heart failure, a heart attack or stroke in the prior 180 days, recent GLP-1 use, or severe kidney disease. Participants weren't especially heavy: the median BMI was 28.6, per Vascular News's report from the ACC presentation.

What STRIDE found

The main result: semaglutide improved maximum walking distance at week 52 by a ratio of 1.13 (95% CI 1.06 to 1.21) compared with placebo, meaning about 13% more distance, with p=0.0004, per the ACC summary. Novo Nordisk's release put the mean treatment difference at 39.9 meters on the steep-incline treadmill.

Source: ACC (ratios), Novo Nordisk release (meters, safety).

Is 40 meters meaningful? The baseline median maximum walking distance was only 186 meters. Lead investigator Dr. Marc Bonaca noted that the 40-meter mean gain exceeded the 10 to 20 meters usually considered clinically important in PAD, as reported by Vascular News. He also pointed to the weak link between weight loss and walking improvement, plus an increase in ankle-brachial index, as suggesting a direct effect on blood vessels. That's a hypothesis, not a proven mechanism.

The same report describes a post-hoc analysis in which fewer semaglutide patients died or needed revascularization for worsening symptoms (14 vs. 30). Post-hoc findings weren't part of the trial's planned testing and shouldn't be treated as proof.

Regulatory status: EU vs. US

Europe. On June 23, 2025, Novo Nordisk announced that the European Medicines Agency's CHMP had adopted a positive opinion to update the Ozempic label with the STRIDE data, and said it expected the European Commission to act within about two months, per the company release. The release did not give the exact label wording, and this guide does not cover the final EU product information.

United States. The same release said Novo Nordisk had filed for a US label expansion with a decision expected in the last quarter of 2025. But the current Ozempic label on DailyMed (revised May 2026) lists three indications, all in adults with type 2 diabetes:

1. Improving blood sugar control, with diet and exercise.
2. Reducing the risk of major cardiovascular events (heart attack, stroke, cardiovascular death) in people with established cardiovascular disease.
3. Reducing the risk of kidney decline, kidney failure, and cardiovascular death in people with chronic kidney disease.

The label's clinical studies section covers the glycemic-control trials, the SUSTAIN 6 cardiovascular outcomes trial and the FLOW kidney trial. It doesn't include STRIDE or any walking-distance data. So don't let anyone tell you Ozempic is "FDA-approved for PAD." It isn't, as of October 2026.

That said, a man with type 2 diabetes and PAD already falls within Ozempic's approved use for blood sugar control. The cardiovascular indication covers adults with type 2 diabetes and established cardiovascular disease; whether your PAD history fits it is your doctor's call. STRIDE adds evidence about walking, not a new reason to be eligible.

Who STRIDE does and doesn't apply to

Source: ACC: STRIDE inclusion and exclusion criteria.

One crossover worth knowing for men 65 and older: the Medicare GLP-1 Bridge lists symptomatic PAD plus a BMI of 27 or higher as one of its eligibility routes for weight-management GLP-1s, per Medicare.gov. The Bridge excludes people with type 2 diabetes, so it's for men with PAD who don't have diabetes. That is coverage for weight treatment, not proof that the drug treats PAD in people without diabetes.

The test to ask for: ankle-brachial index

If you get calf or thigh pain when walking that eases with rest, ask for an ABI. It compares blood pressure at your ankle with your arm using a cuff and a handheld ultrasound, and it's painless. Per the NHLBI:

• A healthy ABI is 1.00 or greater.
• Below 0.90 may indicate PAD.
• Below 0.40 indicates severe PAD.
• If ankle arteries are too stiff to measure (common with diabetes), a toe-brachial index below 0.7 is abnormal.
• An exercise ABI that drops by 20% or more after walking is abnormal, which helps when resting results are borderline.

The NHLBI also recommends asking about testing if you have risk factors, even without symptoms.

Semaglutide doesn't replace the basics

STRIDE compared semaglutide with placebo. It doesn't make semaglutide a substitute for standard PAD care. The core PAD treatments on the NHLBI treatment page still apply:

• Quit smoking. The NHLBI calls smoking the main risk factor for PAD.
• Supervised exercise. Usually at least three sessions a week for 3 to 9 months, mostly treadmill walking, sometimes through cardiac rehab. Home-based walking programs aim for at least 30 minutes of continuous walking.
• Medicines. Antiplatelets such as aspirin or clopidogrel, statins, ACE inhibitors or ARBs for blood pressure, and sometimes cilostazol for walking symptoms.
• Procedures. Angioplasty, stents, or bypass for severe symptoms or limb-threatening disease.

Where this guide stops

This article summarizes one trial and current label status. It isn't a PAD treatment plan. The STRIDE numbers here come from the ACC summary, Novo Nordisk's release, and conference reporting; the full Lancet paper contains subgroup analyses not covered here. Compounded semaglutide is not FDA-approved and was not what STRIDE tested.

Questions to bring to your doctor

• "Should I have an ABI, or an exercise ABI, given my leg symptoms and risk factors?"
• "I have type 2 diabetes and PAD. Does the STRIDE evidence change which diabetes medicine makes sense for me?"
• "Am I on a statin and antiplatelet therapy, and is supervised exercise therapy available to me?"
• "If I don't have diabetes, what evidence is there for a GLP-1 in my situation?"

Sources

1. American College of Cardiology: STRIDE trial summary (Bonaca MP, et al. Lancet 2025)
2. Novo Nordisk press release (via BioSpace): Ozempic 1.0 mg shown to improve walking distance in adults with type 2 diabetes and PAD (March 29, 2025)
3. Novo Nordisk: Ozempic receives EU recommendation in peripheral arterial disease (June 23, 2025)
4. DailyMed: Ozempic (semaglutide) injection label, revised May 2026
5. Vascular News: ACC.25: Semaglutide improves walk distance for PAD patients with diabetes
6. NHLBI: Peripheral Artery Disease
7. NHLBI: PAD causes and risk factors
8. NHLBI: PAD diagnosis
9. NHLBI: PAD treatment
10. Medicare.gov: Medicare GLP-1 Bridge

Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.