Semaglutide Plus Metformin Versus Metformin Alone For Antipsychotic-Induced Weight Gain In Patients With Type 2 Diabetes Mellitus

Abstract

To determine whether combination therapy (semaglutide + metformin) is more efficacious than monotherapy (metformin alone) in reducing the risk of antipsychotic-induced weight gain (AIWG) in patients with Type 2 Diabetes Mellitus (T2DM). This was a single-center, retrospective study evaluating patients ≥ 18 years of age receiving care at Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) from January 2021 to December 2022. Subjects were identified by use of antipsychotic (quetiapine, risperidone, paliperidone, olanzapine, clozapine) with concomitant use of monotherapy or combination therapy. Key exclusion criteria included other medications impacting weight, unstable medical illness, active substance use disorder, and dual antipsychotic use. The primary endpoint was defined as weight loss ≥ 5% from baseline. Secondary outcomes included BMI % difference and HbA1c difference from baseline. Data was analyzed using descriptive statistics. 31 patients were evaluated in each group for the final analysis. 38.7% (12/31) of patients in the monotherapy group achieved the primary outcome of weight loss ≥ 5% from baseline vs. 61.29% (19/31) in the combination group (p = 0.04). For secondary outcomes, the BMI % difference from baseline in the monotherapy group was -3.88% vs. -5.58% in the combination group (p = 0.129). The monotherapy group had a difference in HbA1c % from baseline of 0.14% vs -0.9% in the combination group (p = 0.007). Among T2DM patients on antipsychotics, more patients in the combination group achieved weight loss ≥ 5% within the study period compared to metformin monotherapy. Future research should account for non-diabetic patients, assess lifestyle factors, and exclude other psychotropic medications that may affect weight.

Keywords: Antipsychotics; Diabetes; Metformin; Semaglutide; Veterans; Weight gain.