Semaglutide shows promise in addressing metabolic risk in patients with schizophrenia

People with schizophrenia spectrum disorders have a higher risk of heart and metabolic diseases. Antipsychotics, such as clozapine, which is available as a generic and sold under the brand names Clozaril and Versacloz, and olanzapine, which is also available as a generic and sold under brand names — Zyprexa and Zyprexa Zydis — effectively treat mental health symptoms but are closely associated with weight gain, high blood sugar and increased risk of developing Type 2 diabetes. Results from a clinical trial reported in JAMA Psychiatry suggest that semaglutide, a glucagon-like peptide 1 (GLP-1), may offer a meaningful early intervention strategy to mitigate these risks. Semaglutide is sold as Ozempic as a diabetes therapy and as Wegovy for weight loss.

People with schizophrenia have two to three times higher mortality rates and a life expectancy that is approximately 15 years shorter than people without the disease. High rates of cardiovascular disease are the main case. The cause of the increased risk of cardiovascular disease is multifactorial. Genetics, health behaviors and the metabolic side effects, which include weight gain and poor glucose, of the second-generation antipsychotics, a group of drugs that includes clozapine and olanzapine.

Traditional add-on therapies to deal with the metabolic side effects, such as metformin or topiramate, haven’t been shown to be of much help, producing weight loss of approximately four to 13 pounds and having a mixed effect on hemoglobin A1c (HbA1c). This highlights the necessity for developing more efficacious interventions that are compatible with concurrent antipsychotic therapy.

Marie R. Sass, M.D., Ph.D., of the Mental Health Centre Copenhagen, Copenhagen University Hospital, and now withNovo Nordisk, which makes semaglutide, and her team led a multicenter, double-blind, placebo-controlled trial that enrolled 73 adults, ages 18 to 65, at three clinical sites in Denmark. All participants had schizophrenia spectrum disorders and had started clozapine or olanzapine therapy within the past five years. Importantly, they exhibited early-stage glycemic abnormalities, defined as HbA1c levels between 5.4% and 7.4%, but hadn’t taken any diabetes medications.

The researchers randomly assigned the study participants to receive either once-weekly subcutaneous semaglutide (1 milligram) or placebo for 26 weeks, in addition to their ongoing antipsychotic regimen. The primary end point was observed change in HbA1c from baseline to week 26, with secondary outcomes including weight, waist circumference, fat mass and cardiometabolic markers.