Summary: In a Diabetes Care randomized trial, Semaglutide significantly improved insulin sensitivity, reduced insulin resistance, lowered fasting glucose, and promoted substantial weight loss in patients with antipsychotic-induced metabolic disturbances. Key reported results included Participants (56% women, mean age 38.3 years) provided complete insulin data in 131 cases.
PICO Summary
| Element | Detail |
|---|---|
| Population | 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, HOMA2 of β-cell function, HOMA2 of insulin sensitivity, HOMA of insulin resistance, and body weight. |
| Intervention | 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. |
| Comparison | 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. |
| Outcome | 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 < 0.001), improved insulin sensitivity (8.60 [5.82, 13.65]; P = 0.001), and lowered insulin resistance (-0.69 [-1.00, -0.20]; P = 0.006). Mean weight loss was 9.2 kg and mediated improvements in insulin sensitivity (estimate 7.82; P = 0.01) and insulin resistance (estimate -0.75; P = 0.01). Nonsignificant trends… |
Semaglutide Effects on Insulin Sensitivity and β-Cell...
Primary RCT · Diabetes & glycaemia
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...
Expert Commentary
This Diabetes Care randomized trial evaluated 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. The abstract describes the study as follows: 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, HOMA2 of β-cell function, HOMA2 of insulin sensitivity, HOMA of… The main reported results were: 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 < 0.001), improved insulin sensitivity (8.60 [5.82, 13.65]; P = 0.001), and lowered insulin resistance (-0.69 [-1.00, -0.20]; P = 0.006). Mean weight loss was 9.2 kg and mediated improvements in insulin… The authors conclude: 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… The clinical value of the result depends on whether the trial population, comparator, follow-up and outcome match the..
References
Ganeshalingam AA, Uhrenholt N, Arnfred S, et al.. 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. 2026-May-01. doi:10.2337/dc25-2041. PMID: 41778920.