SOUL Study Demonstrates Cardiovascular Benefit in Type 2 Diabetes

      Presented at ACC 2025, the SOUL trial evaluated the cardiovascular safety and efficacy of oral semaglutide in individuals with type 2 diabetes at high cardiovascular risk. This double-blind, placebo-controlled study included 3,411 participants, comparing once-daily oral semaglutide (14 mg) with placebo over a median follow-up of 3.6 years.

      The primary outcome, a three-point major adverse cardiovascular event (MACE) composite—cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke—was significantly reduced by 18% in the semaglutide group compared to placebo (HR 0.82; 95% CI 0.68–0.98). The benefit was consistent across key subgroups, including individuals with and without established cardiovascular disease.

      Key secondary outcomes showed favorable trends for heart failure hospitalizations and all-cause mortality, although not statistically significant. Glycemic control improved with semaglutide, along with reductions in body weight and systolic blood pressure. The safety profile was consistent with previous GLP-1 RA trials, with gastrointestinal events being the most common adverse effects.

      The SOUL trial confirms that oral semaglutide not only meets cardiovascular safety standards but also offers meaningful risk reduction, supporting its use in high-risk type 2 diabetes populations.