Semaglutide: The First Anti-Obesity Agent Shown to Decrease Cardiovascular Events

The anti-obesity agent, semaglutide (2.4 mg/week) was evaluated in a large (n=17,604) multinational randomized trial called SELECT to examine its effects on cardiovascular (CV) outcomes in overweight/obese patients with preexisting CV disease and no diabetes. The primary outcome of SELECT trial was a composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke. Over a mean duration of follow-up of 39.8 months, a primary CV outcome occurred in 6.5% in the semaglutide group and 8.0% in the placebo group; hazard ratio (HR) 0.80 (95% CI, 0.72 to 0.90; P<0.001). Mean change in body weight over 104 weeks was -9.4% and -0.9% with semaglutide and placebo, respectively; estimated treatment difference (ETT) -8.5% (95% CI, -8.5 to -8.3). There was significant amelioration in blood pressure and plasma levels of lipids, glycated hemoglobin (HbA1c), and C- reactive protein (CRP). The incidences of diabetes and prediabetes were reduced by 73% and 67%, respectively with semaglutide. 16.6% of patients discontinued semaglutide due to adverse effects, mainly gastrointestinal (GI) compared with 8.2% who discontinued placebo (P<0.001). In conclusion, semaglutide is the first anti-obesity agent shown to decrease CV events in overweight/obese subjects with CV disease without diabetes. Further studies are needed to examine the impact of semaglutide on CV events in obese subjects without underlying CV disease.