Semaglutide significantly improved insulin sensitivity and reduced insulin resistance in schizophrenia patients on antipsychotics, with 9.2 kg weight loss partly mediating the metabolic improvements.
9.2 kg weight lossSemaglutide produced substantial weight loss in schizophrenia patients, partly mediating insulin sensitivity improvements
What the researchers found
Semaglutide reduced fasting glucose (-0.87 mmol/L, p<0.001), improved insulin sensitivity (p=0.001), reduced insulin resistance (p=0.006), and achieved 9.2 kg weight loss. Weight loss mediated insulin sensitivity (p=0.01) and resistance (p=0.01) improvements.
Why it matters
Schizophrenia patients lose 15-20 years of life expectancy, largely from metabolic disease caused by their medications. Semaglutide directly addresses this life-threatening side effect.
How the study worked
30-week double-blind RCT (NCT05193578) with 154 participants randomized to semaglutide (n=77) or placebo (n=77), 91.5% completion rate, assessing metabolic parameters with mediation analysis for weight loss.
What this study cannot tell us
Single semaglutide dose (titrated to 1.0 mg or max tolerated). 30-week duration. β-cell function did not improve. Psychiatric outcomes not primary endpoints.
How to read the evidence
Well-designed double-blind RCT with high completion rate and mediation analysis. Strong evidence for this specific population.
When this study was published
Published in 2025.
The bigger picture
This establishes GLP-1 drugs as a solution for antipsychotic-induced metabolic syndrome, potentially saving lives in the schizophrenia population.
Questions still open
- Would higher semaglutide doses produce greater metabolic benefits?
- Does improving metabolic health in schizophrenia patients improve psychiatric outcomes?
- Should semaglutide be co-prescribed with all metabolically harmful antipsychotics?
Common questions
Can semaglutide help with antipsychotic weight gain?
Does improving metabolism help with schizophrenia?
Read the original research
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.
Diabetes care
Citation
Ganeshalingam, Ashok A; Uhrenholt, Nicolai; Arnfred, Sidse; Gæde, Peter; Pedersen, Andreas K; Bilenberg, Niels; Frystyk, Jan. (2026). 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.. Diabetes care. https://doi.org/10.2337/dc25-2041