STRIDE: Semaglutide improves function, symptoms, and outcomes in patients with peripheral artery disease and type 2 diabetes

Semaglutide demonstrated improved walking capacity and quality-of-life and reduced symptoms in patients with type 2 diabetes and symptomatic peripheral artery disease (PAD). The safety profile of semaglutide in the current STRIDE trial was consistent with the agent’s safety profile as observed in prior studies.

STRIDE was a phase 3b double-blind, randomised-controlled trial (NCT04560998) done at 112 outpatient clinical trial sites in 20 countries. Adult participants with type 2 diabetes and Fontaine stage IIa symptomatic PAD (n=792) were randomised 1:1 to 1.0 mg semaglutide once weekly, subcutaneously administered, or placebo, to assess the effect of the drug on the functional capacity of the study population [1]. The primary endpoint was the change in maximal walking distance (MWD) from baseline to week 52. Prof. Marc P. Bonaca (University of Colorado, CO, USA) presented the late-breaking results.

At week 52, the ratio to baseline in MWD was 1.21 in the semaglutide arm and 1.08 in the placebo arm, representing a significant difference between the 2 study arms (Δ1.13; 95% CI 1.06–1.21; P=0.0004). These results corresponded to a clinically meaningful improvement on prospective internal anchor measure that reflected the participants view of whether the improvement observed was meaningful. The benefit in the semaglutide group was apparent early and the separation between groups continued over time. “Participants in the semaglutide arm walked on average 40 metres further than participants in the placebo arm on a constant load treadmill at 2 miles per hour with a 12-degree incline, which reflects clinically meaningful improvement,” said Prof. Bonaca. Furthermore, quality-of-life outcomes and haemodynamic measurements were significantly improved with semaglutide arm compared with placebo (see Figure). Interestingly, an exploratory composite endpoint of rescue initiation, major adverse limb events (MALE), or all-cause mortality also pointed towards the benefit of semaglutide over placebo (HR 0.46; 95% CI 0.24–0.84). Finally, the safety profile of semaglutide was consistent with previous reports, most notably displaying an increased rate of gastrointestinal events compared with placebo (20% vs 6%).

Figure: Primary and secondary outcomes of STRIDE [1]



ABI, ankle brachial index; CI, confidence interval; MWD, maximal walking distance; PFWD, pain-free maximal walking distance.

In summary, semaglutide improved function, symptoms, and haemodynamics, and was associated with lower rates of rescue therapy compared with placebo in patients with type 2 diabetes and PAD. Future studies are needed to further elucidate mechanisms of benefit and to assess the efficacy and safety in patients with PAD without type 2 diabetes.

1. Bonaca MP, et al. STRIDE: Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes: a phase 3b, double-blind, randomized, placebo-controlled trial. Late-breaking Clinical Trials I, ACC 2025 Scientific Session, 29–31 March, Chicago, USA.

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Posted on 22 May 202522 May 2025