Semaglutide safe for schizophrenia patients with prediabetes, obesity

Weekly treatment with semaglutide yields reductions in HbA1c and weight in schizophrenia patients with prediabetes and obesity without worsening mental health, according to a study.

The study included 154 adult patients (mean age 38.3 years, 56.5 percent female) with schizophrenia receiving second-generation antipsychotic medication, who had an HbA1c of 5.7 percent to 6.4 percent, and had a BMI of 27 kg/m². These patients were randomly assigned to receive once-weekly subcutaneous semaglutide (n=77) or placebo (n=77) for 30 weeks. Semaglutide was titrated up to 1.0 mg/week over 8 weeks.

Change in HbA1c was evaluated as the primary endpoint. Secondary endpoints included changes in body weight, schizophrenia symptoms based on Positive and Negative Syndrome Scale 6 (PANSS-6) score, and physical and mental quality of life (QoL) assessed using the second version of the 36-item Short Form Survey.

A total of 141 patients (91.5 percent) completed the trial, including 74 in the semaglutide group and 67 in the placebo group. Compared with placebo, semaglutide reduced HbA1c by 0.46 percent of total haemoglobin (95 percent confidence interval [CI], −0.56 to −0.36) and body weight by 9.21 kg (95 percent CI, −11.68 to −6.75).

Significantly more patients in the semaglutide vs placebo group achieved an HbA1c of <5.7 percent of total haemoglobin (81 percent vs 19 percent; p<0.001). Semaglutide was also associated with greater improvements in high-density cholesterol (difference, 10.81 mg/dL, 95 percent CI, 2.70–18.53; p=0.007) and triglycerides (difference, −29.20 mg/dL, 95 percent CI, −55.75 to 2.65; p=0.03) compared with placebo.

Physical QoL score improved by 3.75 points (95 percent CI, 1.52–5.98) with semaglutide vs placebo (p=0.001), whereas mental QoL and PANSS-6 scores did not significantly differ between the treatment groups.

Gastrointestinal symptoms such as nausea, abdominal pain, and constipation occurred more frequently among semaglutide-treated patients, but these decreased over time. A few patients in the semaglutide group had a high number of hospitalizations, 68 admissions among 15 patients as opposed to 47 hospitalizations among 24 patients in the placebo groups. The frequency of serious adverse effects was similar between the treatment groups.