Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials

Semaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve ≥5% or ≥10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving ≥10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132).