Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial.

Summary

In 792 patients with symptomatic PAD and T2D, weekly semaglutide 1.0 mg for 52 weeks significantly increased maximum walking distance versus placebo (treatment ratio 1.13; p=0.0004). Safety was acceptable with low rates of serious treatment-related adverse events and no treatment-related deaths.

Key Findings

• Semaglutide increased maximum walking distance at 52 weeks vs placebo (estimated treatment ratio 1.13; 95% CI 1.06–1.21; p=0.0004).
• Median ratio to baseline MWD: 1.21 with semaglutide vs 1.08 with placebo.
• Serious treatment-related adverse events were infrequent (1–2%) with no treatment-related deaths.

Clinical Implications

Consider semaglutide to improve functional capacity in patients with PAD and T2D alongside guideline-directed therapies and supervised exercise; monitor GI adverse events.

Limitations

• Population restricted to T2D with Fontaine IIa PAD (ability to walk >200 m), limiting generalizability to more severe PAD or non-diabetic PAD
• Mechanisms of benefit and effects in non-diabetic PAD were not addressed

Future Directions

Assess mechanisms (e.g., endothelial function, inflammation, microvascular perfusion) and efficacy/safety in PAD without diabetes; compare with other GLP-1RA and SGLT2i for functional endpoints.