ADA 2025: Semaglutide Shows Promise in Improving Mobility for Patients With Diabetes and Peripheral Arterial Disease

In the phase 3, multinational, double-blind, randomized STRIDE clinical trial, semaglutide (Ozempic, Rybelsus, Wegovy; Novo Nordisk), a glucagon-like peptide-1 receptor agonist (GLP-1), showed potential in managing peripheral arterial disease (PAD) among individuals with type 2 diabetes (T2D). The findings, shared in a panel discussion titled “Diabetes and Peripheral Artery Disease—Evolving Role of GLP-1 RA and New Insights from the STRIDE Trial,” presented at the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Illinois, taking place June 20 through June 23, demonstrated that semaglutide can significantly improve walking distance, reduce disease progression, and potentially modify the course of PAD.¹

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

The panelists included Verma; Zaina Albalawi, MD, MSc, FRCPC, from Memorial University of Newfoundland; Neda Rasouli, MD, from the University of Colorado School of Medicine; and Alice YY Cheng, MD, FRCPC, from Trillium Health Partners. Together, the experts highlighted critical study findings, including a 40-meter improvement in maximum walking distance on a constant load treadmill and consistent benefits across different patient subgroups, regardless of diabetes duration, body mass index (BMI), or glycemic control.¹

Diabetes and PAD Epidemiology

Algawi began the session by emphasizing the importance of understanding the relationship between diabetes and PAD, a condition where the arteries narrow or become blocked, restricting blood flow—usually in the legs and feet. She highlighted the growing public health concern of diabetes and PAD, with projected diabetes rates rising to 134% in Africa and 87% in the Middle East by 2045.^1,2

Individuals with both diabetes and PAD face significantly higher risks, with a 45% increase in all-cause mortality and a 51% increase in cardiovascular death. Algawi shared unique risk factors for each condition, including age, diabetes, smoking, microvascular disease, and elevated triglycerides for PAD; and age, obesity, genetics, environmental factors, elevated cholesterol, prediabetes, and gestational diabetes for T2D.¹

Lower limb amputations also remain a persistent problem. Algawi noted, "We haven't really made a big dent in this particular outcome, which matters to people living with diabetes."¹

"The principal goals of diabetes care are to reduce the risk of complications, keep people safe, and support self-management," Algawi emphasized.¹

She concluded by underscoring the urgent need for innovative interventions like the STRIDE trial’s approach with semaglutide, which provides new insights and potential solutions for improving outcomes in individuals with diabetes and PAD.¹

Introduction to the STRIDE Trial and Semaglutide's Effects

Verma outlined the significance of the STRIDE trial in addressing the recalcitrant problem of PAD in individuals with diabetes, particularly given the distal nature of the disease and the limited interventional or surgical solutions available. The cardiometabolic effects of semaglutide suggested it might benefit individuals with PAD, prompting the study to explore whether it could improve function, symptoms, hemodynamics, or even lower rates of rescue therapy.¹

A total of 792 individuals (median age 68 years; 25% female) with T2D and PAD presenting with intermittent claudication were randomly assigned to receive either semaglutide (n = 396) or placebo (n = 396) over 52 weeks.^1,2

The results demonstrated that semaglutide significantly improved walking outcomes, enhanced quality of life, and reduced the risk of disease progression by 54%. At week 52, the estimated median ratio to baseline in maximum walking distance was 1.21 in the semaglutide group versus 1.08 in the placebo group.^1,2

Semaglutide was well tolerated, with no treatment-related deaths and a low rate of serious adverse events (1%), consistent with its established safety profile. Importantly, benefits were observed independently of baseline A1C levels, diabetes duration, treatment intensity, BMI, or concurrent use of sodium-glucose cotransporter-2 (SGLT2) inhibitors.^1,2

“The totality of data now suggests that in people with diabetes, semaglutide favorably affects the pipes [atherosclerosis], pump [heart failure], and 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 said in the news release.²

Subgroup Analysis of the STRIDE Trial

Rasouli presented a post hoc analysis of the STRIDE trial, examining the effect of T2D characteristics on semaglutide’s efficacy. The analysis explored whether improvements in walking distance were consistent across subgroups defined by diabetes duration, BMI, glycemic control, and concurrent medication use.¹

Subgroups were based on clinically meaningful thresholds: diabetes duration greater than or less than 10 years; A1C above or below 7%; BMI above or below 30 kg/m²; and concurrent use of glucose-lowering medications, including SGLT2 inhibitors or insulin.¹

The findings showed that the beneficial effects on both maximum and pain-free walking distance were consistent across all subgroups.¹

“These patients are able to walk at least two laps of a soccer field without any pain,” Rasouli noted, emphasizing the real-world impact.¹

These results further support semaglutide’s efficacy and safety profile across the spectrum of T2D, including in individuals who are non-obese or have well-controlled glycemia.¹

Conclusion and Clinical Implications

Cheng concluded the session by discussing the clinical implications of the STRIDE trial for endocrinologists and diabetologists, underscoring its potential to improve outcomes in patients with diabetes and PAD. She encouraged health care providers to consider incorporating semaglutide into practice to enhance functional outcomes and quality of life.¹

However, Cheng also cautioned that further research is necessary to validate the benefits of GLP-1 RAs in individuals with PAD who do not have diabetes.¹

“The reason why this is an important topic to discuss is because some people have looked at the STRIDE study and said, ‘Wow, this is peripheral arterial disease. Does this actually impact my world, and how is this going to change my practice?’ Hopefully, by the end of this, you will have a sense of the approach that you're going to want to take with this,” she concluded.¹

REFERENCES

1. Verma S., Albalawi Z., Rasouli N., Cheng A. “Diabetes and Peripheral Artery Disease—Evolving Role of GLP-1 RA and New Insights from the STRIDE Trial.” Presented: 85th Scientific Sessions of the American Diabetes Association; June 21, 2025; Chicago, Illinois.

2. Semaglutide Increases Walking Capacity in Patients with Peripheral Artery Disease and Type 2 Diabetes. American Diabetes Association. News release. June 21, 2025. Accessed June 21, 2025.