STRIDE: Semaglutide Reduces Progression of PAD by 54% in Type 2 Diabetes

New data from the STRIDE trial suggest the benefits of semaglutide 1.0 mg (Ozempic) on peripheral artery disease (PAD) in people with type 2 diabetes could be even more substantial than the initial trial indicated.

A subanalysis of the trial presented at the 85th Scientific Sessions of the American Diabetes Association (ADA 2025), results shed further light on the benefit seen in the trial, which new data suggests was presented regardless of HbA1c level, SGLT2 inhibitor use, duration of diabetes, and other factors.1

“These findings indicate that clinicians can now recognize semaglutide as a vascular protective medication, with benefits that extend beyond lowering weight or A1C,” said Professor Subodh Verma, MD, PhD, FRCSC, FAHA, FCAHS, cardiovascular surgeon, University of Toronto, Toronto, Canada, and senior author of the STRIDE trial.2

Originally presented at the American College of Cardiology 2025 Annual Scientific Sessions and funded by Novo Nordisk, STRIDE was a double-blind, randomized, placebo-controlled study initiated in 2020 to evaluate the effects of semaglutide 1.0 mg on walking distance in patients with type 2 diabetes PAD. Conducted in 20 countries, the trial enrolled and randomized 792 patients in a 1:1 ratio to receive semaglutide or placebo for 52 weeks.3

The study population had a median age of 68.0 (IQR, 61.0 to 73.0), median BMI of 28.7 kg/m² (IQR, 25.6 to 33.0), 75% were male, and 68% were White. Baseline assessment of disease information indicated 61% had a duration of diabetes of 10 years or longer, and 59% had a BMI of less than 30 kg/m².3

The primary endpoint, the ratio from baseline in maximum walking distance at 52 weeks, favored semaglutide (1.21 [interquartile range, 0.95–1.55] vs 1.08 [0.86–1.36]), with an estimated treatment ratio (ETR) of 1.13 (95% CI, 1.06–1.21; P = .0004). Secondary outcomes further supported semaglutide’s benefit. At week 52, the improvement in walking distance was greater (ETR, 1.08; P = .038), quality-of-life scores (VascuQoL-6) were significantly higher (median difference, 1.00; P = .011), and pain-free walking distance (ETR, 1.11; P = .0046) also improved more with semaglutide than with placebo therapy.3

At ADA 2025, Verma presented a subanalysis of the trial demonstrating use of semaglutide was associated with significantly improved walking outcomes in people with PAD and diabetes, enhanced quality of life, and reduced the risk of disease progression by 54%. Verma also highlighted an estimated median ratio to baseline in maximum walking distance was 1.21 in the semaglutide group compared to 1.08 in the placebo group at week 52.1

Additionally, efficacy data indicated the effects of semaglutide observed in the study were independent of baseline glycemic control, duration of diabetes, or intensity of diabetes, with further data suggesting the effects were consistent across BMI categories and irrespective of background SGLT2 inhibitor use.1

Verma also presented additional safety data from the trial. These data demonstrated semaglutide was well tolerated, with no treatment-related deaths and a safety profile consistent with prior data from the agent.1

“The totality of data now suggest that in people with diabetes, semaglutide favorably affects the pipes [atherosclerosis], pump [heart failure], filter [kidney outcomes]. And, in patients with PAD, these new data provide robust evidence that semaglutide is a therapy to improve their function, quality of life, and progression of disease,” Verma added.2

References:

1. Verma S. Diabetes and Peripheral Artery Disease—Evolving Role of GLP-1 RA and New Insights from the STRIDE Trial. Presented at: 85th American Diabetes Association Scientific Sessions. June 20 – 23, 2025. Chicago, Illinois.

2. American Diabetes Association. Semaglutide Increases Walking Capacity in Patients with Peripheral Artery Disease and Type 2 Diabetes | American Diabetes Association. Diabetes.org. Published June 21, 2025. Accessed June 21, 2025. https://diabetes.org/newsroom/press-releases/semaglutide-increases-walking-capacity-patients-peripheral-artery-disease

3. Campbell P. STRIDE: Semaglutide Improves Functional Outcomes in Peripheral Artery Disease. HCP Live. Published March 29, 2025. Accessed June 21, 2025. https://www.hcplive.com/view/semaglutide-improves-functional-outcomes-in-peripheral-artery-disease