Ozempic Significantly Improves Walking Distance in Patients with Type 2 Diabetes and Peripheral Artery Disease
Key Insights
Phase 3 STRIDE trial results show Ozempic (semaglutide) 1 mg increased maximum walking distance by 13% compared to placebo in patients with type 2 diabetes (search) and peripheral artery disease (search).
Patients treated with semaglutide experienced a clinically meaningful median improvement of 26.4 meters in walking distance on a 12% incline, along with better pain-free walking and quality of life measures.
Based on these positive findings, Novo Nordisk has submitted a label extension application to the FDA, potentially making Ozempic the first new medication in over two decades to improve functional outcomes in PAD patients.
Semaglutide 1 mg, marketed as Ozempic by Novo Nordisk, demonstrated significant improvements in walking distance for patients with type 2 diabetes (search) and peripheral artery disease (search) (PAD), according to new data presented at the American College of Cardiology's Annual Scientific Session in Chicago.
The phase 3b STRIDE trial results, simultaneously published in The Lancet, showed that once-weekly semaglutide 1 mg increased maximum walking distance by 13% compared to placebo at 52 weeks, meeting the study's primary endpoint.
Significant Functional Improvements
The double-blind, randomized, placebo-controlled trial enrolled 792 adults (mean age 68 years, 25% women) with type 2 diabetes (search) and symptomatic PAD. All participants had intermittent claudication (search) and an ankle-brachial index of 0.9 or less or a toe-brachial index of 0.7 or less.
"Importantly, we selected patients that had Fontan IIa stage disease, which is the earliest manifestation of symptoms," said Dr. Marc P. Bonaca, executive director of CPC Clinical Research and CPC Community Health, and lead investigator of the STRIDE trial. "Despite that, they were severely disabled. Even patients who have early-stage PAD by clinical classification were limited [at baseline] to 185 m of walking on a treadmill, which is about one-tenth of a mile before they had to stop."
The primary endpoint results showed the estimated median ratio to baseline in maximum walking distance on a constant load treadmill at 52 weeks was 1.21 in the semaglutide group compared with 1.08 in the placebo group (estimated treatment ratio, 1.13; 95% CI, 1.06-1.21; p=0.0004).
Compared with placebo, the semaglutide group had a median improvement in maximum walking distance from baseline to 52 weeks of 26.4 meters (95% CI, 11.8-40.9), representing a clinically meaningful difference.
"To put that into context, a change on a flat 6-minute walk test that would be clinically significant for this population would be 20 meters," Dr. Bonaca explained. "This is double that, and it's on a 12% grade, so it's walking up a hill."
Comprehensive Benefits Beyond Walking Distance
The trial also demonstrated superiority to placebo for all confirmatory secondary outcomes, including pain-free walking distance (estimated treatment ratio vs placebo 1.11; 95% CI, 1.03 to 1.20; p=0.0046) and Vascular Quality of Life Questionnaire-6 (VascuQoL-6) scores (estimated treatment difference vs placebo 1.00; 95% CI, 0.48 to 1.52; p=0.011) at 52 weeks.
Additional metabolic benefits were observed in the semaglutide group compared to placebo, including greater reductions in body weight (estimated treatment difference, −4.1 kg; p<0.0001), HbA1c (estimated treatment difference, −1 percentage point; p<0.0001), and systolic blood pressure (estimated treatment difference, −3.2 mm Hg; p=0.0042) at 52 weeks.
"Even patients who had a BMI below the median had a consistent benefit with semaglutide," noted Dr. Bonaca, indicating the drug's effects extend beyond weight loss.
Clinical Implications for a Significant Unmet Need
PAD is a form of atherosclerotic cardiovascular disease that affects approximately 12 million people in the United States, with one in four also having type 2 diabetes (search). The presence of type 2 diabetes increases the incidence of PAD and accelerates disease progression and severity.
"Peripheral artery disease (search) may cause severe symptoms, physical limitations, and a diminished quality of life, often making even short walks—such as retrieving the mail—challenging," Dr. Bonaca said. "In individuals with PAD and diabetes, the disease can be even more severe, affecting small blood vessels and limiting the effectiveness of revascularization procedures and other treatments."
In an exploratory clinical analysis, the outcome of rescue initiation (defined as a new medication or revascularization), major adverse limb events, and mortality at 52 weeks favored the semaglutide group (HR = 0.46; 95% CI, 0.24-0.84).
Safety Profile
The safety profile of semaglutide in the STRIDE trial was consistent with previous studies. Serious adverse events were reported in 19% of participants in the semaglutide arm and 20% in the placebo arm. Serious adverse events that were possibly or probably treatment-related occurred in 1% and 2% of participants, respectively.
The most frequent serious adverse event across both groups was gastrointestinal events (1% in both groups). No treatment-related deaths were reported.
Regulatory Implications
Based on the STRIDE trial data, Novo Nordisk has submitted a label extension application for Ozempic to the U.S. Food and Drug Administration. A decision is anticipated in 2025.
"We have a new drug for PAD," Dr. Bonaca concluded. "And it adds a new element to our understanding of GLP-1 (search) receptor agonists."
If approved, semaglutide would be the first medication in over two decades to show meaningful improvements in functional capacity and quality of life for patients with both PAD and type 2 diabetes (search), addressing a critical unmet need in this patient population.
"The results from STRIDE, the first and only dedicated PAD functional outcomes trial with a GLP-1 (search) RA treatment, provide important clinical insights that help further our understanding and approach to cardiometabolic diseases like type 2 diabetes (search) and peripheral artery disease (search)," said Dr. Michael Radin, Executive Medical Director of Diabetes Medical Affairs at Novo Nordisk, Inc.