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In this episode, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, explored two key trial updates in type 2 diabetes (T2D) care at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions.

SOUL, a double-blind, placebo-controlled, event-driven trial, was designed to assess the cardiovascular effects of oral semaglutide (Rybelsus) in patients with T2D and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). A total of 9650 patients aged ≥50 years were enrolled across 450 centers in 44 countries.

Analyses showed oral semaglutide (Rybelsus) was linked to a 14% reduction in major adverse cardiovascular events (MACE) in high-risk patients with T2D. This reduction included the incidence of cardiovascular (CV) death, myocardial infarction (MI), or stroke compared to placebo (HR, 0.86; 95% CI, 0.77 to 0.96; P = .006) over a median follow-up of 47.5 months.

A 26% reduction in non-fatal MI was the primary driver of benefit, while safety findings identified gastrointestinal adverse events as more common with oral semaglutide. Based on these results, Novo Nordisk announced plans to pursue regulatory approval for a label expansion of oral semaglutide to include MACE risk reduction in adults with T2D and established CV disease.

STRIDE, a double-blind, randomized, placebo-controlled trial initiated in 2020, assessed the effects of semaglutide 1.0 mg (Ozempic) on functional outcomes, including walking distance, in patients with T2D and peripheral artery disease (PAD). Conducted across 112 sites in 20 countries, the trial randomized 792 patients to receive semaglutide or placebo for 52 weeks.

Analyses showed semaglutide use was associated with improvements in maximal walking distance, quality of life, and ankle-brachial index (ABI). SOUL met its primary endpoint, with semaglutide favoring the ratio from baseline in maximum walking distance at 52 weeks (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).

At week 57, the improvement in walking distance was higher with semaglutide (ETR, 1.08; P = .038). Quality-of-life scores (VascuQoL-6) at week 52 were significantly higher in the semaglutide group (median difference, 1.00; P = .011), as were improvements in pain-free walking distance (ETR, 1.11; P = .0046).

Editor’s Note: In this episode, there was an error in the discussion about the new dosing for Rybelsus in the SOUL trial. The corrected information is that the 14 mg dose is now 9 mg with the new formulation, due to improved absorption. The full corrected statement is: “Instead of 3 mg, the new dose is 1.5 mg; instead of 7 mg, it’s 4 mg; and instead of 14 mg, it’s 9 mg.”