Diabetes Care
Semaglutide improves insulin sensitivity in patients with schizophrenia and prediabetes
The 30‑week randomized, placebo‑controlled HISTORI trial found that once‑weekly semaglutide 1.0 mg significantly improved insulin sensitivity and reduced fasting glucose among adults with schizophrenia, prediabetes, and obesity receiving second‑generation antipsychotics. Semaglutide recipients experienced a greater drop in fasting glucose (–0.87 mmol/L) and a meaningful improvement in insulin sensitivity compared with placebo, with benefits largely mediated by substantial weight loss (mean –9.2 kg). Improvements in β‑cell function were observed but weren’t statistically significant.
Clinical takeaway: Consider semaglutide as an adjunct metabolic intervention for patients with schizophrenia receiving second‑generation antipsychotics who present with obesity or prediabetes, as it may significantly improve insulin sensitivity and reduce cardiometabolic risk.
Source:
Ganeshalingam AA, et al. (2026, March 4). Diabetes Care. Semaglutide Effects on Insulin Sensitivity and β-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly. https://pubmed.ncbi.nlm.nih.gov/41778920/