Efficacy and Safety of Semaglutide for Managing Antipsychotic-associated Weight Gain: A Systematic Review and Meta-analysis.

Antipsychotic medication-induced weight gain (AIWG) is a difficult-to-manage condition. Semaglutide is a widely used weight-lowering agent, but its role in AIWG has been evaluated in only few studies. This SRM evaluated if semaglutide can be effectively and safely used for AIWG in schizophrenia, bipolar disorder, and other psychiatric diseases. Electronic databases were searched for articles evaluating the use of semaglutide for managing AIWG. The primary outcome was reduction in body weight. Secondary outcomes were changes in body mass index (BMI), waist circumference (WC), HBA1c, metabolic parameters, and adverse events. Data from nine studies (44,233 participants; 4.21% diabetes; 94.79% euglycemia) which fulfilled all criteria were analysed. Semaglutide for AIWG was associated with a significant reduction in weight [mean difference (MD) -7.37 kg (95% confidence interval (CI): -12.39, -2.35); P < 0.001; I2 = 99%], BMI [MD -2.76 kg/m2 (95% CI: -4.15, -1.37); P < 0.001; I2 = 98%], WC [MD -5.12 cm (95% CI: -7.21, -3.03); P < 0.001; I2 = 76%], HbA1c [MD -0.35% (95% CI: -0.47, -0.24); P < 0.001; I2 = 91%] and higher >5% weight loss [OR 2.25 (95% CI: 2.14, 2.36); P < 0.001; I2 = 0%]. The occurrence of nausea, diarrhoea, and injection site reactions was similar. Vomiting was significantly higher in semaglutide users. The occurrence of psychiatric adverse events was lower in semaglutide users but not significant [OR 0.59 (95% CI: 0.33-1.07); P = 0.08; I2 = 0%]. Semaglutide has good efficacy data with regard to quantum of weight loss with good safety for managing AIWG.