Oral Semaglutide Shows Broad Cardiometabolic Benefits in Type 2 Diabetes Trial

Oral semaglutide improved multiple cardiometabolic metrics among adults with type 2 diabetes at high risk for atherosclerotic cardiovascular disease, according to a post hoc secondary analysis of the SOUL trial. Once-daily oral semaglutide reduced risk for major adverse CV events by 14% compared with placebo among adults with type 2 diabetes at high risk for atherosclerotic CVD, with many cardiovascular benefits observed at just 13 weeks of treatment.

Adults receiving semaglutide had an estimated 3.19 mm Hg greater decline in systolic blood pressure from baseline to 13 weeks compared with placebo. There was an estimated 3.7 mm Hg larger decrease in pulse pressure in the semaglutide group compared with placebo at 13 weeks, with similar differences between the two groups seen at 156 weeks.

The semaglutide group had larger decreases in total cholesterol, non-HDL cholesterol and triglycerides at both 13 weeks and 156 weeks compared with the placebo group. HDL cholesterol was lower for the semaglutide group than for the placebo group at 13 weeks, but at 156 weeks, adults receiving the study drug had a higher HDL cholesterol than those receiving placebo. The semaglutide group had lower LDL cholesterol than those receiving placebo at 13 weeks, but not at 156 weeks.

At 13 weeks, adults receiving semaglutide had a 0.82 percentage point greater decrease in HbA1c and a 2.28 percentage point larger decline in body weight than the placebo group. At 156 weeks, oral semaglutide conferred a 0.47 percentage point larger drop in HbA1c and a 3.26 percentage point greater decrease in body weight than placebo. A greater improvement in high-sensitivity C-reactive protein at 13 and 104 weeks was observed with semaglutide compared with placebo.

The SOUL trial included 9,650 adults aged 50 years and older with type 2 diabetes plus at least one of coronary heart disease, cerebrovascular disease, symptomatic peripheral artery disease or chronic kidney disease. Participants were randomly assigned to once-daily oral semaglutide titrated up to 14 mg or placebo plus standard of care.

The observed CV risk factor benefits may contribute to the overall benefit of oral semaglutide on outcomes for major adverse CV events, providing supporting evidence for the use of oral semaglutide for CV risk reduction. These cardiovascular benefits appeared even before substantial weight loss, suggesting direct drug effects of oral semaglutide beyond HbA1c lowering and weight reduction.

Ozempic is a once-weekly injectable glucagon-like peptide-1 receptor agonist whose active pharmaceutical ingredient is semaglutide. It is a prescription medication approved for the treatment of adults with type 2 diabetes mellitus to improve glycemic control and to reduce the risk of major adverse cardiovascular events in those with established cardiovascular disease or high risk factors. Pivotal studies such as SUSTAIN-6 and PIONEER-6 have consistently shown that semaglutide reduces the composite endpoint of major adverse cardiovascular events, which includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, in patients with type 2 diabetes and either established cardiovascular disease or high risk factors.