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
Authors' conclusion
Semaglutide significantly improved insulin sensitivity, reduced insulin resistance, lowered fasting glucose, and promoted substantial weight loss in patients with antipsychotic-induced metabolic disturbances. Weight loss partly mediated the metabolic improvements, while β-cell function remained largely unchanged. These findings support semaglutide as a potential strategy for mitigating metabolic dysfunction in this high-risk population.
Study context
- Population
- Overweight or obese individuals with schizophrenia and prediabetes receiving second-generation antipsychotics; 56% women, mean age 38.3 years141 completed
- Participants
- 154 participants
- Comparison
- Semaglutide vs placebo
- Semaglutiden = 77
- Placebon = 77reference
Methodological detailsdouble-blind, placebo-controlled
- Double-blind
- Placebo-controlled
Primary result
As reported in the abstract
Insulin sensitivity, insulin resistance and fasting glucose vs placebo · 30 weeks
Each group vs placeboDifference in fasting glucose, mmol/L (95% CI)P value
Semaglutide
−0.87(−1.15 to −0.59)
P < 0.001Each group vs placeboEstimate (95% CI)P value
Semaglutide
difference in insulin sensitivity (HOMA2) 8.60(5.82–13.65)
P = 0.001Semaglutide
difference in insulin resistance (HOMA) −0.69(−1.00 to −0.20)
P = 0.006Further findings
Weight loss and its mediation of insulin sensitivity and insulin resistance improvements
- Mean weight loss
- 9.2 kg
- Weight loss mediated improvement in insulin sensitivity
- estimate 7.82; P = 0.01
- Weight loss mediated improvement in insulin resistance
- estimate −0.75; P = 0.01
Fasting insulin, C-peptide and β-cell function
- Fasting insulin: nonsignificant trend toward reduction
- −52.3 pmol/L; P = 0.11
- C-peptide: nonsignificant trend toward reduction
- −182.9 pmol/L; P = 0.096
- β-cell function: modest, nonsignificant increase
- 8.10; P = 0.19
Original publication
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. Published 4 March 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →