Semaglutide effects on insulin sensitivity and beta-cell function in patients with schizophrenia, prediabetes, and obesity treated with second generation antipsychotics

Objective To examine the effects of semaglutide on insulin sensitivity, resistance, and beta-cell function, and to explore whether these changes were mediated by weight loss in overweight or obese individuals with schizophrenia and prediabetes receiving second-generation antipsychotics (SGAs). Research Design and Methods In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n=77) or placebo (n=77); 141 (91.5%) completed the study. Baseline and end-of-study assessments included fasting glucose, insulin, C-peptide, beta-cell function (HOMA-B), insulin sensitivity (HOMA-2S), insulin resistance (HOMA-IR), and body weight. Results Participants (56% women, mean age 38.3 years) provided complete insulin data in 131 cases. Compared with placebo, semaglutide significantly reduced fasting glucose (-0.87 mmol/L; 95% CI [-1.15, -0.59]; p