TOPLINE:

Among patients with schizophrenia, prediabetes, and overweight or obesity who were on stable treatment with second‑generation antipsychotics, once-weekly semaglutide led to greater improvements in insulin sensitivity than placebo, with the improvements largely mediated by substantial weight loss.

METHODOLOGY:

• Researchers conducted a clinical trial to examine whether semaglutide improves glucose-metabolic outcomes in 154 patients with schizophrenia, prediabetes, and overweight or obesity who were on stable treatment with second-generation antipsychotics.
• Patients received either once-weekly injection of semaglutide (uptitrated up to 1.0 mg; n = 77; mean age, 39.1 years; 45% women) or a similar volume of placebo (n = 77; mean age, 37.6 years; 68% women) for 30 weeks.
• Fasting blood samples were collected at baseline and week 30 to measure glucose, insulin, and C-peptide levels; insulin sensitivity and resistance and beta-cell function were estimated from these measures.
• Changes in fasting glucose levels, insulin sensitivity and resistance, and beta-cell function were evaluated from baseline to week 30, and the mediation analysis assessed whether weight loss explained the observed effects.

TAKEAWAY:

• Compared with placebo, semaglutide reduced fasting glucose levels by 0.87 mmol/L (P < .001), increased insulin sensitivity by a mean of 8.60 units (P = .001), and lowered insulin resistance by a mean of 0.686 units (P = .006).
• The mean weight loss was 9.2 kg with semaglutide vs placebo; the mediation analysis indicated that the weight loss largely explained the improvement in insulin sensitivity (P = .01).
• Beta-cell function increased with semaglutide, but the change was not statistically significant; fasting insulin and C-peptide levels tended to fall, but those declines were also not significant.

IN PRACTICE:

"Given the high prevalence of insulin resistance and cardiovascular risk in schizophrenia, semaglutide may represent a valuable strategy for mitigating metabolic dysfunction in this at-risk population," the authors wrote.

SOURCE:

This study was led by Ashok A. Ganeshalingam, Odense University Hospital, Odense, Denmark. It was published online on March 04, 2026, in Diabetes Care.

LIMITATIONS:

The findings may not be generalisable to all patient populations, particularly those not receiving concurrent antipsychotic treatment. The sample size may have been insufficient to detect smaller but clinically meaningful changes in beta-cell function and fasting insulin levels. Moreover, the study duration was limited to only 30 weeks.

DISCLOSURES:

The trial was funded by Region Sjælland, Steno Diabetes Center Zealand, Aase og Ejnar Danielsens Fond, the Novo Nordisk Foundation, and Steno Diabetes Center Odense. Several authors reported receiving PhD salaries, research grants, travel support, or lecture fees or participating on industry advisory boards of various foundations and pharmaceutical companies, including some of the study funders.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.