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Semaglutide and Walking Capacity in People With Symptomatic Peripheral Artery Disease and Type 2 Diabetes - STRIDE
Contribution To Literature:
The STRIDE trial demonstrated that semaglutide significantly improves function, symptoms, and health-related QoL in patients with symptomatic PAD and T2DM.
Description:
The goal of the phase 3b trial was to evaluate the safety of once-weekly injections of the GLP-1 receptor agonist semaglutide and to determine whether it improves function (symptoms and quality of life [QoL]) in patients with symptomatic peripheral artery disease (PAD) and type 2 diabetes (T2D) with functional limitations.
Study Design
Participants from 112 outpatient sites in 20 countries in North America, Asia and Europe were randomly assigned (1:1) to receive subcutaneous semaglutide 1.0 mg once per week for 52 weeks or matching placebo injection (n=396 for both semaglutide and placebo groups).
- Total number of enrollees: 792
- Duration of follow-up: 57 weeks
- Mean patient age: 68 years
- Percentage female: 24.5%
Inclusion criteria:
- Age ≥18 years
- T2DM diagnosis ≥180 days prior to screening
- Hemoglobin A1c ≤10%
- Early-stage symptomatic PAD (Fontaine stage IIa)
- Pain-free walking distance ≥200 m on a flat treadmill test
- Maximum walking distance ≤600 m on a constant load treadmill test
- Ankle-brachial index ≤0.9 or toe-brachial index ≤0.7
Exclusion criteria:
- Conditions other than PAD that limit walking
- Planned orthopedic leg surgery or surgery affecting walking ability
- Vascular revascularization within 180 days prior to screening or planned arterial revascularization
- Heart failure (NYHA class III-IV)
- Myocardial infarction, stroke, hospitalization for unstable angina, or TIA within 180 days prior to screening
- Current or previous treatment with any GLP-1 receptor agonist within 90 days prior to screening
- Estimated GFR <30 mL/min/1.73 m2 measured within the previous 6 months
Principal Findings:
Primary outcome: The primary endpoint was the estimated ratio of the maximum walking distance (MWD) at week 52 when compared with baseline, as measured on a graded treadmill walking test. During study conduct, the estimated ratio of median change from baseline in MWD (in meters) was 1.13 (95% CI, 1.06-1.21), p=0.0004, favoring semaglutide over placebo.
Secondary outcomes: The risk of serious adverse events was low, and there were no treatment-related deaths. When evaluating the confirmatory secondary endpoints using estimated treatment ratios (with 95% CI), results showed:
- Change in MWD from baseline to week 57: 1.08 (1.00-1.16), p=0.038
- Change in Vascular QoL Questionnaire-6 from baseline to week 52: 1.00 (0.48-1.52), p=0.011
- Change in pain-free walking distance on constant load treadmill from baseline to week 52: 1.11 (1.03-1.20), p=0.0046
Interpretation:
The results of the STRIDE trial showed that semaglutide was associated with a higher estimated ratio of MWD in patients with symptomatic PAD and T2DM. With confirmatory secondary endpoints, the change in MWD, change in quality of life, and symptom improvement were also improved with semaglutide vs. placebo. With an excellent safety profile, the use of semaglutide is supported by these functional improvements in all patients with PAD and T2DM.
References:
Bonaca MC, Catarig AM, Houlind K, et al., for the STRIDE Trial Investigators. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomized, placebo-controlled trial. Lancet 2025;Mar 29:[Epub ahead of print].
Presented by Dr. Marc P. Bonaca at the American College of Cardiology Annual Scientific Session (ACC.25), Chicago, IL, March 29, 2025.
Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)
Keywords: ACC25, ACC Annual Scientific Session, Diabetes Mellitus, Type 2, GLP-1 Receptor, Peripheral Arterial Disease, Vascular Diseases
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