OBJECTIVE: The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse cardiovascular events, in patients with established cardiovascular disease and overweight or obesity. METHODS: Safety data focused on serious adverse events (SAEs), all adverse events (AEs) leading to permanent treatment discontinuation irrespective of seriousness, and prespecified AEs of special interest irrespective of seriousness. Tests of treatment differences were determined by two-sided p values. RESULTS: The proportion of patients with SAEs was lower with semaglutide versus placebo (33.4% vs. 36.4%
p <
0.001), primarily driven by cardiac disorders (11.5% vs. 13.5%
p <
0.001). The proportion of patients with AEs leading to discontinuation was higher with semaglutide versus placebo (16.6% vs. 8.2%
p <
0.001), a difference driven by gastrointestinal disorders (10.0% vs. 2.0%)
however, proportions due to SAEs leading to discontinuation were similar (3.6% vs. 4.1%). Suicide/self-injury SAEs were low and balanced between groups (0.11% in both groups). Gallbladder-related disorders were more frequent with semaglutide versus placebo (2.8% vs. 2.3%
p = 0.04), mainly driven by cholelithiasis (1.4% vs. 1.1%), whereas proportions of cholecystitis were similar between groups (0.6% vs. 0.6%). CONCLUSIONS: The long-term safety profile observed in the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) study is consistent with previously reported semaglutide studies. No new safety concerns were identified for once-weekly semaglutide 2.4 mg.