Sex Differences in Effectiveness of Semaglutide in Patients with Peripheral Artery Disease: The STRIDE Trial

Abstract

Background: Peripheral artery disease (PAD) is prevalent in women and men with type 2 diabetes (T2D). Sex-based differences exist in its epidemiology, clinical presentation, functional impact, outcomes, and potentially in responses to treatments. Recently, semaglutide 1.0 mg has been shown to improve functional outcomes and health-related quality of life (QoL) in individuals with early symptomatic PAD and T2D in the STRIDE trial.

Objectives: To describe baseline characteristics, functional status, and therapeutic efficacy of once-weekly semaglutide 1.0 mg between females and males with PAD and T2D as a post-hoc analysis from the STRIDE trial.

Methods: The primary endpoint in STRIDE was the ratio to baseline in maximum walking distance (MWD) at week 52 on a constant load treadmill. Confirmatory secondary endpoints included change in MWD at week 57, change in pain-free walking distance (PFWD) at week 52, and change in PAD-specific vascular quality of life (VascuQoL-6) total score from baseline to week 52. Herein, we report the outcomes analyzed by sex.

Results: Of 792 participants, 195 (24.6%) were female and 597 (75.4%) were male. Females were younger, had lower rates of smoking, lower prevalence of concomitant coronary artery disease and heart failure, and less frequent use of antiplatelet therapies compared to males. Geometric mean MWD at baseline was 187.3 meters (coefficient of variation [CV] 0.6) and 191.5 meters (CV 0.6) in females and males, respectively. At week 52, there was a consistent improvement in MWD across sexes, which favored semaglutide treatment (p-interaction value=0.65). At week 57, there was a consistent trend for improved MWD that favored semaglutide treatment for both females and males (p-interaction value=0.53). Improvement in PFWD was consistent across sexes at week 52 in favor of semaglutide (p-interaction value=0.80). Likewise, PAD-specific QoL (assessed by VascuQOL-6) improvements with semaglutide in both sexes were consistent with the overall trial.

Conclusions: In this post-hoc analysis from STRIDE, semaglutide 1.0 mg exhibited consistent improvements in functional outcomes in people with early symptomatic PAD and T2D regardless of sex. Females with PAD demonstrated differences in baseline demographics, and treatment patterns compared to males, highlighting the importance of sex-specific evaluation in PAD trials.

Keywords: Glucagon-like peptide-1 receptor agonist; Peripheral Artery Disease; STRIDE; Type 2 Diabetes; semaglutide; sex-based differences.