Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

This randomized, double blind, placebo controlled trial (PIONEER 6) evaluated the cardiovascular safety of once daily oral semaglutide, a GLP1 receptor agonist, in 3183 patients with type 2 diabetes at high cardiovascular risk. Over a median follow up of 15.9 months, oral semaglutide demonstrated noninferiority to placebo for the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.79; 95% CI 0.57–1.11; P<0.001 for noninferiority). Notably, it reduced cardiovascular deaths by 51% (HR 0.49; 95% CI 0.27–0.92) and all cause mortality by 49% (HR 0.51; 95% CI 0.31–0.84). While gastrointestinal side effects led to higher discontinuation rates (11.6% vs. 6.5%), serious adverse events were less frequent with semaglutide (18.9% vs. 22.5%). The study confirms oral semaglutide’s cardiovascular safety profile, aligning with subcutaneous GLP1 agonists, and suggests potential mortality benefits.

This randomized, double blind, placebo controlled trial (PIONEER 6) evaluated the cardiovascular safety of once daily oral semaglutide, a GLP1 receptor agonist, in 3183 patients with type 2 diabetes at high cardiovascular risk. Over a median follow up of 15.9 months, oral semaglutide demonstrated noninferiority to placebo for the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.79; 95% CI 0.57–1.11; P<0.001 for noninferiority). Notably, it reduced cardiovascular deaths by 51% (HR 0.49; 95% CI 0.27–0.92) and all cause mortality by 49% (HR 0.51; 95% CI 0.31–0.84). While gastrointestinal side effects led to higher discontinuation rates (11.6% vs. 6.5%), serious adverse events were less frequent with semaglutide (18.9% vs. 22.5%). The study confirms oral semaglutide’s cardiovascular safety profile, aligning with subcutaneous GLP1 agonists, and suggests potential mortality benefits.