Semaglutide shows significant vascular benefits in PAD patients with type 2 diabetes, STRIDE trial confirms

What did the STRIDE clinical trial reveal about semaglutide’s impact on walking ability in patients with PAD and type 2 diabetes?

At the 85th Scientific Sessions of the American Diabetes Association (ADA), held from June 20 to 23, 2025, in Chicago, a pivotal analysis from the STRIDE clinical trial revealed that semaglutide significantly enhances walking capacity and slows the progression of peripheral artery disease (PAD) in patients with type 2 diabetes. The American biotech firm behind the trial presented these findings during a late-breaking symposium, simultaneously published in Diabetes Care. This trial adds a critical layer of evidence to semaglutide’s growing reputation as a therapy with cardiovascular and vascular benefits beyond its original use in glycemic control and weight loss.

The STRIDE trial evaluated 792 adult patients with confirmed PAD and type 2 diabetes across 112 outpatient clinical sites spanning 20 countries. Over a 52-week period, participants were randomized into two groups: 396 patients received semaglutide while another 396 were assigned a placebo. All participants experienced intermittent claudication, a symptom of PAD involving pain during physical exertion, and demonstrated low ankle-brachial or toe-brachial index scores indicative of restricted blood flow.

By week 52, patients treated with semaglutide saw a median walking distance ratio of 1.21 from baseline, compared to 1.08 for those in the placebo group. These results not only confirm symptom improvement but also reflect meaningful functional gains, a key metric for patients struggling with PAD-related disability.

How does semaglutide reduce disease progression in patients with peripheral artery disease and diabetes?

One of the most notable outcomes from the STRIDE sub-analysis was a 54% reduction in the risk of PAD progression among patients administered semaglutide. PAD is a chronic condition that narrows arteries and restricts blood flow, affecting over 230 million people worldwide and nearly one-third of diabetes patients. Without effective intervention, PAD often leads to disability, limb amputation, and increased mortality. The STRIDE findings suggest that semaglutide could play a protective role in halting or slowing this progression, thereby potentially preventing serious downstream complications.

The American biotech company emphasized that the benefits of semaglutide were observed across key clinical subgroups. Results were consistent irrespective of baseline A1C levels, diabetes duration, body mass index (BMI), or whether patients were also on SGLT2 inhibitors. This suggests that semaglutide’s vascular benefits may be robust enough to be effective across diverse metabolic profiles, an encouraging development for clinicians managing complex cases of cardiometabolic disease.

Experts presenting at the ADA 2025 conference noted that these outcomes mark a rare and much-needed advancement in PAD treatment, an area that has seen little therapeutic innovation in more than 25 years. Analysts following the trial have characterized the findings as a potential inflection point in the clinical use of GLP-1 receptor agonists.

What is the safety profile of semaglutide in this patient population and were there any treatment-related deaths?

According to data from STRIDE, semaglutide was well tolerated over the course of the 52-week study. There were no treatment-related deaths, and serious adverse events occurred in only 1% of patients receiving the therapy. This aligns with the known safety profile of semaglutide from previous trials in obesity and diabetes management, including cardiovascular outcomes trials such as SELECT and SUSTAIN.

The favorable safety data strengthens the argument for semaglutide’s wider adoption in treating vascular complications in diabetes, including PAD. For institutional investors and healthcare providers alike, this reinforces the potential for semaglutide to generate incremental clinical value without introducing disproportionate risk, particularly in older populations with multiple comorbidities.

During the ADA symposium, Professor Subodh Verma, cardiovascular surgeon at the University of Toronto and senior author of the trial, summarized the broader implications by stating that semaglutide offers benefits for the “pipes, pump, and filter”—referring to atherosclerosis, heart failure, and kidney disease. This triple-effect framing may influence how prescribers think about the drug’s systemic utility.

How are institutional stakeholders reacting to semaglutide’s new vascular data from the STRIDE trial?

Institutional sentiment surrounding semaglutide continues to be strong, with the STRIDE data adding new clinical use cases that could support label expansions or inclusion in updated treatment guidelines. While financial figures tied to semaglutide’s PAD application have yet to be disclosed, analysts have pointed to the sizeable market opportunity in managing comorbid PAD and diabetes—a segment historically underserved in therapeutic innovation.

Given that PAD affects more than 230 million individuals globally and up to 30% of the diabetic population, semaglutide’s expansion into this space could drive further uptake. Institutional observers expect increased clinician interest, especially if additional regulatory discussions or label updates are initiated based on the STRIDE data.

While semaglutide is already approved for chronic weight management and glycemic control in type 2 diabetes, this vascular evidence could encourage broader payer acceptance and drive formulary updates to include PAD as a potential indication—subject to future regulatory filings and outcomes research.

What is the future research direction for semaglutide in PAD and non-diabetic populations?

The STRIDE trial provides a foundational layer for exploring semaglutide’s application in other PAD populations, including individuals without diabetes. While the current trial was limited to those with confirmed type 2 diabetes, researchers presenting at ADA 2025 indicated that further studies may examine semaglutide’s role in vascular function independent of glucose regulation.

The ADA’s 85th Scientific Sessions provided a high-visibility platform for these revelations, drawing thousands of experts in diabetes care and cardiovascular medicine. The growing interest in GLP-1 receptor agonists as systemic therapies—not just glucose-lowering agents—is reflected in both research investment and clinician adoption patterns.

Future research is likely to focus on mechanistic studies exploring how semaglutide interacts with vascular endothelial function and inflammatory markers that contribute to PAD progression. This could further validate its position in the expanding class of cardiometabolic therapeutics with multiple organ benefits.

For stakeholders in drug development and chronic disease care, the STRIDE data may serve as a catalyst for additional investment in multipurpose therapies capable of addressing interconnected pathologies such as diabetes, obesity, atherosclerosis, and heart failure.

How does the ADA Scientific Sessions shape the clinical and strategic positioning of emerging diabetes therapies?

The ADA’s annual Scientific Sessions remains one of the most influential platforms for shaping clinical guidance in diabetes care. The 2025 event in Chicago drew global attention as the forum for unveiling pivotal data like the STRIDE trial. In addition to showcasing research, the event also contributes to sentiment-building among clinicians, researchers, and biopharma investors.

As the American Diabetes Association celebrates 85 years of advancing science and patient care, its annual event continues to serve as a barometer for therapeutic innovation. The STRIDE trial data on semaglutide’s impact on PAD is emblematic of the session’s broader theme—leveraging existing diabetes drugs to target secondary complications and improve holistic outcomes.

With an estimated 136 million Americans living with diabetes or prediabetes, therapies like semaglutide that address multiple endpoints could reshape standard-of-care protocols in coming years. Analysts expect follow-up trials and real-world data to further refine the drug’s positioning in PAD management, while global regulators may assess its eligibility for expanded indications.