“In medicine, we often measure what we can, but rarely what matters most to the patient. The STRIDE trial helps bridge that gap.”
Peripheral artery disease (PAD) remains one of the most common—and disabling—manifestations of atherosclerotic disease, particularly in people living with type 2 diabetes. Yet for all our advances in reducing major adverse cardiovascular events, we’ve had remarkably few tools to improve walking capacity, symptom burden, and quality of life in this population.
Enter the STRIDE trial, led by our colleagues and friends Marc Bonaca and Josh Beckman and published this week in The Lancet.
STRIDE (Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes) was a multicenter, randomized, placebo-controlled phase 3b trial enrolling 792 participants with Fontaine stage IIa PAD and type 2 diabetes. Participants were assigned to receive once-weekly semaglutide 1.0 mg or placebo for 52 weeks.
The Findings
The results were both statistically and clinically meaningful:
• Primary Endpoint:
The median increase in maximum walking distance at 52 weeks was 13% higher in the semaglutide group compared to placebo. This translated to a median improvement of 26.4 meters and a mean of nearly 40 meters on a constant-load treadmill test (12% grade).
• Pain-Free Walking Distance:
Increased by 29.8 meters (mean difference vs. placebo), indicating true symptomatic relief.
• Quality of Life:
VascuQoL-6 scores improved significantly more with semaglutide, reflecting real-world patient-perceived benefit.
• Exploratory Outcomes:
Fewer participants on semaglutide required rescue therapy or revascularization, and composite outcomes including death or major adverse limb events trended favorably.
• Safety Profile:
Consistent with previous semaglutide trials, with no new safety signals.
Why This Matters
What sets STRIDE apart is not just the positive result—it’s the focus on what matters most to people living with PAD: the ability to walk without pain. The magnitude of benefit with semaglutide was on par with cilostazol, the only current pharmacologic therapy for intermittent claudication in the U.S.—but with cardiometabolic benefits extending well beyond the leg.
And unlike cilostazol, which has limited tolerability and no demonstrated cardiovascular benefit, semaglutide has been repeatedly shown to reduce stroke, MI, heart failure, and even diabetic foot complications.
Looking Ahead
This study may mark a turning point—not just in how we treat PAD, but in how we prioritize function and quality of life as therapeutic goals. While future studies will be needed in broader PAD populations (e.g., without diabetes), the implications are already clear: semaglutide is more than a glucose-lowering drug. It is a functional medicine—in every sense of the word.
Congratulations to Marc Bonaca and the STRIDE team on this important contribution.
Bonaca MP, Catarig AM, Houlind K, et al. “Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE).” Lancet. 2025. DOI:10.1016/S0140-6736(25)00509-4
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