Vol. 5, Issue 1, Part A (2023)

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 obese patients with overweight with preexisting CV disease and no diabetes. The primary outcome 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, and C- reactive protein (CRP). The incidence 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. In conclusion, semaglutide is the first anti-obesity agent shown to decrease CV events in 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.