Semaglutide and walking capacity in symptomatic PAD and type 2 diabetes patients: the STRIDE trial

Selected in The Lancet by Xavier Devoisin

This phase 3b, double-blind, randomised, placebo-controlled trial assessed the effect of semaglutide on walking capacity in patients with symptomatic peripheral artery disease (PAD) and type 2 diabetes.

After 52 weeks of treatment, semaglutide significantly improved maximal walking distance, symptoms, and quality of life compared to placebo. These results also suggest a potential anti-inflammatory effect of semaglutide, supporting its use in this high-risk population.

References:

Authors: Marc P Bonaca, Andrei-Mircea Catarig, Kim Houlind, Bernhard Ludvik, Joakim Nordanstig, Chethana Kalmady Ramesh, Neda Rasouli, Harald Sourij, Alex Videmark, Subodh Verma, STRIDE Trial Investigators

Reference: Lancet. 2025 Mar 28:S0140-6736(25)00509-4

DOI: 10.1016/S0140-6736(25)00509-4

Read the abstract

Objective:

The objective was the comparison of maximum walking distance from baseline to week 52 — semaglutide vs placebo.

Study:

Phase 3b, double-blind, randomised, placebo-controlled clinical trial.

Population:

112 outpatient clinical trial centers, 20 countries in North America, Asia, and Europe
Inclusion: Type 2 Diabetes (T2D) + Stage IIA PAD (> 200m on flat treadmill and < 600m on inclined treadmill)

Outcomes and conclusion:

Significant improvement in function, symptoms, and quality of life, with a potential anti-inflammatory effect in patients with peripheral artery disease and type 2 diabetes.

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

Results of the STRIDE trial – Source: The Lancet

Comments:

Subcutaneous semaglutide 1 mg / week:

13 % improvement in walking distance vs placebo (med 26.4 m / avg 39.9 m)
Improved quality of life (VascuQoL-6 and SF-36 questionnaires)
Fewer rescue treatments vs placebo
Improvement in ankle-brachial index (ABI)
Modest weight loss of 4.1 kg with Semaglutide vs placebo

Key benefits:

Rapid benefit (from week 26) maintained over time (up to week 57)
Improved performance on inclined treadmill
Increased ABI, supporting a direct vascular benefit (anti-inflammatory action)
Potential additional benefits: weight loss, cardiometabolic effects, renal benefits, major cardiovascular event reduction, heart failure benefits

Limitations:

Difficulty translating treadmill improvement to daily life activities
Benefits may vary based on disease severity, functional demands, and patient expectations
Study limited to diabetic patients
Short-term evaluation of adverse major events
Modest but statistically significant improvement in ABI warrants further mechanistic studies on PAD

Other considerations:

Weight loss and gastrointestinal effects may have revealed randomization, but unlikely to affect objective measures (walking distance or ABI)

Other available medications:

Pentoxifylline: Few benefits compared to placebo
Cilostazol: Similar clinical improvement to Semaglutide

Both increase walking distance without impact on cardiovascular health