Semaglutide significantly reduces antipsychotic-induced weight gain by 7.37 kg across diverse psychiatric populations

Antipsychotic medication-induced weight gain (AIWG) is a prevalent and challenging side effect of psychiatric treatments, significantly impacting patient adherence and increasing the risk of cardiometabolic diseases. Current management strategies often fall short, leaving a critical gap in effective interventions. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely recognized for its potent weight-lowering effects in general obesity, prompting investigation into its potential role for AIWG, which often involves complex metabolic dysregulation.

This systematic review and meta-analysis evaluated the efficacy and safety of semaglutide for managing AIWG. Researchers systematically searched electronic databases for studies assessing semaglutide in patients with schizophrenia, bipolar disorder, and other psychiatric conditions experiencing AIWG. Data from nine studies involving 44,233 participants were analyzed. The primary outcome was reduction in body weight, while secondary outcomes included changes in body mass index (BMI), waist circumference (WC), HbA1c, other metabolic parameters, and adverse events.

Semaglutide demonstrated significant efficacy in reducing weight and improving metabolic markers in patients with AIWG.

Semaglutide was associated with a significant reduction in body weight, with a mean difference (MD) of -7.37 kg (95% CI: -12.39, -2.35; P < 0.001; I2 = 99%). This weight loss was accompanied by a reduction in BMI (MD -2.76 kg/m2; 95% CI: -4.15, -1.37; P < 0.001; I2 = 98%) and WC (MD -5.12 cm; 95% CI: -7.21, -3.03; P < 0.001; I2 = 76%). Furthermore, HbA1c levels significantly decreased (MD -0.35%; 95% CI: -0.47, -0.24; P < 0.001; I2 = 91%), and the odds of achieving >5% weight loss were significantly higher with semaglutide (OR 2.25; 95% CI: 2.14, 2.36; P < 0.001; I2 = 0%). While nausea, diarrhea, and injection site reactions were similar to controls, vomiting was significantly higher in semaglutide users. Psychiatric adverse events were non-significantly lower (OR 0.59; 95% CI: 0.33-1.07; P = 0.08; I2 = 0%).