Presentation (CTI)

OBJECTIVES: Originally approved for type 2 diabetes mellitus (T2DM), semaglutide also has efficacy in obesity without T2DM. We compared the safety profile of semaglutide when given to treat obesity with/without T2DM in controlled and real-world settings.
METHODS: Systematic literature review based on a PubMed search.
RESULTS: From an initial pool of 910 articles, 20 records (14 RCTs, 6 RWE studies) including 12,378 patients with obesity (RCT: 12,223 (including the SELECT Trial), RWE: 155) and 14,560 patients with obesity+T2DM (RCT: 1,386; RWE: 13,174) were analysed. Semaglutide demonstrated a favourable safety profile across both controlled trials and real-world settings. In RCTs, 87.8% of participants experienced at least one adverse event (AE), the majority of which were mild (75.2%), followed by moderate (39%) and severe (7%) events. In RWE studies, 31.9% of participants reported one or more AEs, with 19.4% classified as mild, 8.6% as moderate, and only 2.9% as severe. Gastrointestinal (GI) adverse events - such as nausea, diarrhoea, vomiting, abdominal discomfort, and constipation - were most frequently reported in both RCTs (65%) and RWE studies (14.1%). In RCTs, serious adverse events (SAEs) were reported in 10.8% of patients with obesity and 4.9% of those with both obesity and T2DM. The most common SAEs were cardiac (11.7%), followed by infections (6.5%) and neurological events (4.9%). No SAEs were reported in RWE studies. Discontinuation due to AEs ranged 2.1%-17% in patients with obesity and 5%-27% in those with obesity+T2DM in RCTs; in RWE studies, the rates ranged from 5.1%-11.1% for obesity and 2.9% for obesity+T2DM. Two RCTs each reported a single patient death, neither of which was attributed to semaglutide treatment.
CONCLUSIONS: Semaglutide is a safe drug for obesity management among patients with/without T2DM, with a low proportion of SAEs and treatment discontinuation due to AEs, in both controlled and real-world settings.