Semaglutide Improves Walking Capacity in Peripheral Artery Disease: STRIDE Trial

Peripheral artery disease is marked by decreased blood flow to the lower extremities owing to atherosclerotic narrowing of the peripheral arteries. The clinical hallmark of PAD is intermittent claudication, which leads to walking ability and exercise performance restrictions. This is commonly observed in type 2 diabetic patients, where vascular dysfunction is accelerated by metabolic abnormalities. Despite the high disability rate associated with PAD, effective therapeutic agents for walking ability are not readily available.

The analysis was performed post-hoc based on data from a randomized clinical trial (NCT04560998) that was a double-blind, placebo-controlled trial of once-weekly subcutaneous semaglutide 1.0 mg versus a placebo of comparable composition in adults with PAD and T2D experiencing intermittent claudication.

The trial randomized a total of 792 participants, of whom 195 (25%) were female, and had a mean age of 66.6 years with a standard deviation of 9.4 years. The primary endpoint of the current study is the ratio of baseline change in MWD. This endpoint was evaluated after 52 weeks, with a constant load treadmill test performed at a speed of 3.2 km/h and a 12% incline. The confirmatory secondary endpoint is the ratio to baseline change in pain-free walking distance (PFWD), again with the constant load treadmill test.

Key findings:

• The post hoc analysis of the STRIDE randomized clinical trial included 792 patients with PAD and type 2 diabetes.

• The study population was 25% female and had a mean age of 66.6 ± 9.4 years.

• Once-weekly semaglutide 1.0 mg improved walking capacity compared to placebo at 52 weeks.

• The results were 1.16 vs. 0.98 for the ratio to baseline in maximum walking distance in patients with eGFR < 60 mL/min/1.73 m² and 1.25 vs. 1.12 in patients with eGFR ≥ 60 mL/min/1.73 m².

• The results were 1.26 vs. 1.04 in patients who underwent peripheral revascularization and 1.23 vs. 1.11 in those who did not.

• The absolute improvements in maximum walking distance were 83.7 meters vs. 45.0 meters in individuals who still had preserved renal function and 84.9 meters vs. 47.2 meters in participants who were less than 75 years old.

• The improvements were still 60.7 meters vs. 14.6 meters in participants who were 75 years and older and were treated with semaglutide or placebo. Similar results were observed in all polyvascular diseases.

Semaglutide has shown a consistent improvement in walking capacity among individuals suffering from PAD and type 2 diabetes. This improvement has been observed among individuals of different age groups and among those suffering from different clinical manifestations of PAD severity, including impaired renal function, revascularization history, and polyvascular disease. This has shown semaglutide as a promising agent for improving functional capacity among a high-risk population that has few pharmacological options.

Reference:

Joakim Nordanstig, Ecenur Guder Arslan, Andrei-Mircea Catarig, Kim Houlind, Bernhard Ludvik, Neda Rasouli, Harald Sourij, Sebastian Thomas, Subodh Verma, Marc P Bonaca, Semaglutide in peripheral artery disease and diabetes by baseline disease severity and age: the STRIDE trial, European Heart Journal, 2026;, ehag129, https://doi.org/10.1093/eurheartj/ehag129