Drug Update · Cardiology

STRIDE: Semaglutide Increases Walking Distance 1.13-Fold in PAD with T2D

July 16, 2026

Drug

Semaglutide (Ozempic)

Trial

STRIDE (phase 3b, double-blind, randomised, placebo-controlled)

Primary result

Estimated treatment ratio 1·13 (95% CI 1·06-1·21); p=0·0004 [maximum walking distance at week 52 versus placebo]

Comparator

Placebo

Trial dose

Subcutaneous semaglutide 1·0 mg once per week for 52 weeks

Randomised participants

792 (semaglutide n=396; placebo n=396)

Clinical Perspective

This report is relevant to cardiologists, vascular specialists, endocrinologists, and other clinicians managing patients with PAD and type 2 diabetes. The STRIDE data support that semaglutide 1·0 mg weekly improved treadmill-measured walking distance at 52 weeks versus placebo in a population with intermittent claudication and documented PAD ^[1]. Clinicians may consider these trial findings when discussing functional outcomes with patients who have PAD and type 2 diabetes, while noting the safety profile reported in STRIDE and the trial population characteristics (Fontaine stage IIa; able to walk >200 m).

Dr. Kavya Sharma · Cardiology

Semaglutide (Ozempic) increased maximum walking distance at week 52 versus placebo in people with symptomatic peripheral artery disease (PAD) and type 2 diabetes in the phase 3b STRIDE trial, with an estimated treatment ratio 1·13 (95% CI 1·06-1·21; p=0·0004) ^[1]. In STRIDE, participants received subcutaneous semaglutide 1·0 mg once per week or placebo for 52 weeks ^[1]. Clinicians should consult current prescribing information for full dosing guidance.

Clinical Context

Peripheral artery disease is described in the STRIDE publication as a highly morbid atherosclerotic vascular disease of the legs affecting over 230 million individuals globally; few therapies have been shown to improve functional capacity and health-related quality of life in people with lower limb PAD ^[1]. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue marketed as OZEMPIC by Novo Nordisk; the FDA prescribing information characterizes semaglutide as a GLP-1 receptor agonist ^[2]. STRIDE was funded by Novo Nordisk and sought to evaluate whether semaglutide improves walking ability, symptoms, quality of life, and outcomes in patients with PAD and type 2 diabetes ^[1].

Key Findings

The STRIDE trial (phase 3b, double-blind, randomised, placebo-controlled) enrolled 792 participants who were randomly assigned 1:1 to semaglutide (n=396) or placebo (n=396) ^[1]. The primary endpoint was the ratio to baseline of maximum walking distance at week 52 measured on a constant-load treadmill in the full analysis set ^[1]. The estimated median ratio to baseline in maximum walking distance at week 52 was 1·21 (IQR 0·95-1·55) in the semaglutide group versus 1·08 (IQR 0·86-1·36) in the placebo group, yielding an estimated treatment ratio 1·13 (95% CI 1·06-1·21; p=0·0004) in favor of semaglutide ^[1]. Trial inclusion required adults with type 2 diabetes and PAD with intermittent claudication (Fontaine stage IIa, able to walk >200 m) and an ankle-brachial index ≤0·90 or toe-brachial index ≤0·70 ^[1]. Median age was 68·0 years (IQR 61·0-73·0); 195 (25%) participants were female and 597 (75%) were male ^[1]. Dosing in STRIDE was subcutaneous semaglutide 1·0 mg once per week for 52 weeks ^[1].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Six serious adverse events in five (1%) participants in the semaglutide group and nine serious adverse events in six (2%) participants in the placebo group were judged possibly or probably treatment related; the most frequent serious adverse events were serious gastrointestinal events ^[1].
Serious gastrointestinal events: two events reported by two (1%) participants in the semaglutide group and five events reported by three (1%) participants in the placebo group ^[1].
There were no treatment-related deaths reported in STRIDE ^[1].

Study Design

STRIDE was a phase 3b, double-blind, randomised, placebo-controlled trial conducted at 112 outpatient clinical trial sites in 20 countries across North America, Asia, and Europe ^[1]. Adults aged 18 years and older with type 2 diabetes and symptomatic PAD with intermittent claudication (Fontaine stage IIa, able to walk >200 m) and an ankle-brachial index ≤0·90 or toe-brachial index ≤0·70 were eligible; participants were randomly assigned 1:1 using an interactive web response system to receive subcutaneous semaglutide 1·0 mg once per week for 52 weeks or placebo. Clinicians should consult current prescribing information for full dosing guidance. The primary endpoint was the ratio to baseline of maximum walking distance at week 52 measured on a constant-load treadmill in the full analysis set. The trial is registered with ClinicalTrials.gov, NCT04560998, and was funded by Novo Nordisk ^[1].

FAQ

Q1 What did the STRIDE trial show?

A1 The STRIDE trial showed that semaglutide increased maximum walking distance measured on a constant-load treadmill at week 52 versus placebo in people with symptomatic peripheral artery disease and type 2 diabetes. The estimated median ratio to baseline in maximum walking distance at week 52 was 1·21 (IQR 0·95-1·55) with semaglutide versus 1·08 (IQR 0·86-1·36) with placebo, corresponding to an estimated treatment ratio 1·13 (95% CI 1·06-1·21; p=0·0004).

Q2 Who was enrolled in STRIDE?

A2 STRIDE enrolled adults aged 18 years and older with type 2 diabetes and peripheral artery disease presenting with intermittent claudication (Fontaine stage IIa) who were able to walk more than 200 m and had an ankle-brachial index of ≤0·90 or a toe-brachial index of ≤0·70. From Oct 1, 2020, to July 12, 2024, 1363 patients were screened and 792 were randomised 1:1 to semaglutide (n=396) or placebo (n=396). Median age was 68·0 years (IQR 61·0-73·0); 195 (25%) participants were female and 597 (75%) were male.

Q3 What were the side effects in STRIDE?

A3 In the safety analysis of STRIDE, six serious adverse events in five (1%) participants in the semaglutide group and nine serious adverse events in six (2%) participants in the placebo group were judged possibly or probably treatment related, with the most frequent serious adverse events being serious gastrointestinal events (two events in two [1%] semaglutide participants and five events in three [1%] placebo participants). There were no treatment-related deaths reported in STRIDE.

Q4 What does STRIDE mean for clinical practice?

A4 STRIDE provides evidence that semaglutide 1·0 mg once weekly for 52 weeks can increase treadmill-measured walking distance versus placebo in patients with symptomatic PAD and type 2 diabetes meeting the trial criteria. Clinicians should interpret the findings in the context of the trial population (Fontaine stage IIa, able to walk >200 m), the reported safety data, and funding sources. Use of semaglutide in PAD patients not meeting STRIDE criteria or without type 2 diabetes was not studied in STRIDE and was not reported in the provided excerpts. Clinicians should consult current prescribing information for complete dosing guidance.

STRIDE: Semaglutide Increases Walking Distance 1.13-Fold in PAD with T2D

STRIDE: Semaglutide Increases Walking Distance 1.13-Fold in PAD with T2D

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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