A post hoc analysis of the STRIDE trial has found that once-weekly semaglutide 1.0 mg consistently improves functional outcomes in people with early symptomatic peripheral artery disease (PAD) and type 2 diabetes (T2D), irrespective of sex.¹˒²

This analysis addresses the need for sex-specific data in PAD, where differences in epidemiology, clinical presentation, and treatment response are increasingly recognised.

The analysis was conducted on data from the STRIDE trial (NCT04560998), a phase 3b, randomised, double-blind, placebo-controlled study. It included 792 participants (195 female, 597 male) with early symptomatic PAD (Fontaine classification IIa) and T2D. Participants received either once-weekly subcutaneous semaglutide 1.0 mg or a matched placebo for 52 weeks.¹

The primary endpoint was the ratio to baseline in maximum walking distance (MWD) at week 52, measured on a constant load treadmill. Confirmatory secondary endpoints included MWD at week 57 (5 weeks after treatment cessation), pain-free walking distance (PFWD) at week 52, and change in the PAD-specific Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score.¹

At baseline, females were younger and had lower rates of smoking, concomitant coronary artery disease, and heart failure compared with males. Females also had less frequent use of antiplatelet therapies.¹

For the primary endpoint, semaglutide improved MWD at week 52 compared with placebo, with a consistent benefit observed in both females (estimated treatment ratio [ETR] 1.17; 95% CI: 1.02–1.34) and males (ETR 1.13; 95% CI: 1.04–1.22). There was no evidence of heterogeneity of treatment effect by sex (P-interaction=0.65).¹

This trend continued at week 57, with sustained improvements in MWD favouring the semaglutide group in both sexes (P-interaction=0.53). Consistent benefits were also seen for PFWD and VascuQoL-6 scores at week 52, with no significant interaction by sex. The occurrence of adverse events leading to drug discontinuation was low and generally comparable between sexes.¹

These findings suggest that the functional benefits of semaglutide in patients with early symptomatic PAD and T2D extend to both women and men. The study authors concluded that "semaglutide 1.0 mg exhibited consistent improvements in functional outcomes in people with early symptomatic PAD and T2D regardless of sex."¹ They also noted that the observed baseline differences highlight "the importance of sex-specific evaluation in PAD trials."¹

This study was funded by Novo Nordisk A/S, Denmark.

References

1. Verma S, Catarig AM, Houlind K, et al. Sex Differences in Effectiveness of Semaglutide in Patients With Peripheral Artery Disease: The STRIDE Trial. J Am Coll Cardiol. 2025;86(20):1843-1857. https://doi.org/10.1016/j.jacc.2025.08.046

2. Bonaca MP, Catarig AM, Houlind K, et al. 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. Lancet. 2025;405(10489):1580-1593. https://doi.org/10.1016/S0140-6736(25)00509-4

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