Benefit of Semaglutide in Symptomatic Peripheral Artery Disease by Baseline Type 2 Diabetes Characteristics: Insights From STRIDE, a Randomized, Placebo-Controlled, Double-Blind Trial

🥇 Top 1% JournalJun 21, 2025Diabetes care

Semaglutide’s benefits for artery disease symptoms vary with type 2 diabetes traits

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Abstract

Among 792 participants, semaglutide 1.0 mg significantly improved maximum walking distance in individuals with symptomatic peripheral artery disease and type 2 diabetes.

Improvements in walking function were consistent regardless of diabetes duration, BMI, HbA1c level, or diabetes medication use.
Maximum walking distance increased with an estimated treatment ratio of 1.15 for participants with less than 10 years of diabetes and 1.13 for those with 10 or more years.
Pain-free walking distance also showed significant improvement across all subgroups analyzed.
A weak correlation was observed between reductions in BMI and improvements in maximum walking distance, particularly in control individuals with higher baseline BMI.
Safety outcomes remained consistent across different subgroups.

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OBJECTIVE: The Semaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes (STRIDE) trial (NCT04560998) showed that once-weekly subcutaneous semaglutide 1.0 mg significantly improved functional outcomes, symptoms, and quality of life in individuals with symptomatic peripheral artery disease (PAD) and type 2 diabetes. Whether these benefits are consistent across diabetes-related characteristics remains unclear.

RESEARCH DESIGN AND METHODS: The primary outcome was the ratio to baseline (ETR) in maximum walking distance (MWD), with pain-free walking distance (PFWD) as a key secondary end point. Both were measured at 52 weeks using a constant load treadmill. Subgroup analyses were performed by diabetes duration, BMI, HbA1c, and diabetes medications. A mixed model for repeated measurements was used, incorporating treatment, region, and subgroup as fixed factors, and baseline value as covariate, along with the treatment-by-subgroup interaction.

RESULTS: Among 792 participants (median diabetes duration 12.2 years, HbA1c 7.1%, and BMI 28.7 kg/m2), 35.1% used sodium-glucose cotransporter 2 inhibitors and 31.7% used insulin. Semaglutide significantly improved MWD regardless of diabetes duration (ETR of 1.15 vs. 1.13 for <10 vs. ≥10 years, P = 0.80), BMI (1.12 vs. 1.16 for <30 vs. ≥30 kg/m2, P = 0.58), HbA1c (1.13 for <7% and ≥7%, P = 0.99), or medication use. Semaglutide also improved PFWD across subgroups (P > 0.1 for all interactions). BMI reduction correlated weakly with MWD improvements and was more pronounced in the control individuals with higher baseline BMI. Safety outcomes were consistent across subgroups.

CONCLUSIONS: Semaglutide improved walking function in people with PAD and type 2 diabetes, including individuals without obesity and those with well-controlled HbA1c. Benefits were consistent across BMI and HbA1c categories, supporting effectiveness beyond weight or glycemic changes.

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