Semaglutide Significantly Lowers Peripheral Artery Disease Progression in Type 2 Diabetes

In a groundbreaking study presented at the 85th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, recent findings from the STRIDE trial reveal that semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces the progression of peripheral artery disease (PAD) by 54% in patients with type 2 diabetes (T2D). The trial, which included 792 participants across 20 countries, highlights semaglutide's potential as a significant therapeutic intervention not only for glycemic control but also for improving functional outcomes in PAD.

**Context and Significance** Peripheral artery disease, characterized by narrowed arteries reducing blood flow to the limbs, is a common complication in patients with diabetes, leading to severe implications for mobility and quality of life. The STRIDE trial's results emphasize the necessity for comprehensive treatment strategies that address both diabetes management and vascular health. As Dr. Subodh Verma, MD, PhD, FRCSC, FAHA, FCAHS, a cardiovascular surgeon at the University of Toronto and senior author of the study, noted, "Semaglutide represents a vascular protective medication, with benefits extending beyond glycemic control."

**Study Details** The double-blind, randomized, placebo-controlled STRIDE trial commenced in 2020, focusing on the efficacy of semaglutide 1.0 mg (marketed as Ozempic) in enhancing walking distance in T2D patients with PAD. Participants were randomized to receive either semaglutide or a placebo for 52 weeks. The primary endpoint assessed was the change in maximum walking distance from baseline to the end of the trial. Results showed that the semaglutide group had a significant improvement in maximum walking distance (1.21 vs. 1.08) compared to the placebo group, with a P-value of 0.0004, demonstrating a clinically meaningful benefit.

**Expert Analysis** Dr. Verma highlighted that the benefits of semaglutide were consistent across various demographic and clinical subgroups, independent of factors such as baseline HbA1c levels, diabetes duration, and use of SGLT2 inhibitors. The study's secondary outcomes also reinforced semaglutide’s efficacy, with notable improvements in pain-free walking distances and quality-of-life scores measured by the VascuQoL-6 (P = 0.011).

In corroboration of these findings, Dr. Emily Martinez, a diabetes researcher at Duke University, stated, "The comprehensive data from the STRIDE trial suggest that GLP-1 receptor agonists like semaglutide could redefine treatment paradigms for patients with T2D and PAD, offering not only metabolic but also vascular benefits."

**Safety and Tolerability** Safety data presented at the conference indicated that semaglutide was well tolerated among participants, with no treatment-related deaths reported. The adverse events were consistent with previous studies on semaglutide, establishing its safety profile as favorable for long-term use in this patient population. Dr. Patrick Campbell, a clinical researcher at the University of California, San Francisco, emphasized the importance of these findings, stating, "The safety profile of semaglutide reinforces its role as a viable option for clinicians looking to enhance patient outcomes, particularly in a vulnerable population."

**Implications and Future Outlook** The implications of these findings are significant for clinical practice, suggesting that semaglutide could be integrated into broader treatment strategies for managing PAD in T2D patients. The results also pave the way for further research into the vascular effects of GLP-1 receptor agonists, potentially expanding their therapeutic applications.

As the landscape of diabetes management evolves, the STRIDE trial provides compelling evidence that addressing vascular health is integral to improving the quality of life for patients with type 2 diabetes. Health policymakers and clinicians are now urged to consider these findings in treatment protocols, ensuring that patients receive holistic care that encompasses both glycemic control and vascular protection. Moving forward, ongoing studies will be essential to fully elucidate the long-term benefits and applications of semaglutide in various patient populations.