Semaglutide improves walking ability in T2D patients with PAD
ACC.25 – In the STRIDE trial, semaglutide increased the maximum walking distance, reduced symptoms, and improved quality of life at ~1 year compared with placebo in patients with T2D and symptomatic peripheral artery disease (PAD).
This summary is based on the presentation of Marc Bonaca, MD (Aurora, CO, USA) at the ACC.25 Scientific Session - The Effect Of Once-weekly Subcutaneous Semaglutide On Functional Capacity In People With Type 2 Diabetes And Peripheral Artery Disease: Primary Results From The Phase 3b, Randomized, Placebo-controlled, Double Blind Stride Trial.
Introduction and methods
For patients with peripheral artery disease (PAD), there are only few medical therapies that improve functional capacity, and none is prioritized based on their PAD-specific benefits. The study aim was to investigate the effect of semaglutide on functional capacity—as measured by walking ability—symptoms, and patient-reported outcomes and its safety in patients with T2D and PAD.
The STRIDE trial was an international, placebo-controlled, double blind, phase 3b RCT in which 792 patients with T2D and early-stage symptomatic PAD (Fontaine stage IIa, i.e., ability to walk >200 m) were randomized to subcutaneous semaglutide 1.0 mg once weekly or placebo for 52 weeks. The primary endpoint was the ratio to baseline of the maximum walking distance (MWD) at 52 weeks. Confirmatory secondary endpoints were changes from baseline in MWD at 57 weeks, Vascular Quality of Life Questionnaire-6 score at 52 weeks, and pain-free walking distance at 52 weeks.
Main results
- At 52 weeks, the estimated median ratio to baseline of the MWD was larger in patients treated with semaglutide than those receiving placebo (1.21; IQR: 0.95–1.55 vs. 1.08; IQR: 0.86–1.36; estimated treatment ratio (ETR): 1.13; 95%CI: 1.06–1.21; P=0.0004). This was a clinically meaningful improvement based on a prespecified anchor measure (OR: 1.79; 95%CI: 1.32–2.43; P=0.0002).
- The confirmatory secondary endpoints also indicated beneficial effects of semaglutide versus placebo. The ETR to baseline of the MWD at 57 weeks was 1.08 (95%CI: 1.00–1.16; P=0.038), the estimated treatment difference to baseline of the Vascular Quality of Life Questionnaire-6 score at 52 weeks was 1.00 (95%CI: 0.48–1.52; P=0.011), and the ETR to baseline of the pain-free walking distance at 52 weeks was 1.11 (95%CI: 1.03–1.20; P=0.005).
- An exploratory analysis showed a lower incidence of a composite outcome of rescue treatment, all-cause mortality, or major adverse limb events in semaglutide-treated patients compared with placebo-treated patients (4% vs. 8%; HR: 0.46; 95%CI: 0.24–0.84).
- The frequencies of adverse events (122.4 vs. 99.0 events per 100 person-years) and serious adverse events (32.5 vs. 26.9 events per 100 person-years) were similar in the semaglutide and placebo groups.
- There were no treatment-related deaths.
Conclusion
In the STRIDE trial, semaglutide increased the MWD, reduced symptoms, and improved quality of life at ~1 year compared with placebo in patients with T2D and symptomatic PAD. The safety profile of semaglutide was consistent with that observed in previous trials.
- Our reporting is based on the information provided at the ACC.25 Scientific Session -