Metformin, but Not Aripiprazole, Was Associated With Attenuation of Weight Gain in Clozapine-Treated Inpatients With Concurrent Disorders: A Repeated Measures Cohort Analysis: La metformine, mais non l’aripiprazole, a été associée à une atténuation d

BackgroundIndividuals with schizophrenia and concurrent substance use disorders (SUDs) face a high risk of rapid weight gain during residential treatment, driven by inpatient environmental factors, baseline metabolic vulnerability, and metabolically active psychotropic medications. Clozapine, commonly indicated for treatment-resistant psychosis, is frequently associated with early and substantial weight gain. This study examined whether adjunctive metformin or aripiprazole attenuated weight gain in individuals taking clozapine in a naturalistic residential setting.MethodsThis retrospective cohort study included adults prescribed clozapine during admission to a 105-bed provincial concurrent disorders facility in British Columbia, Canada (2021-2024). Adults with ≥90-day admissions and available therapeutic drug monitoring were included. Monthly weights were extracted from electronic records and linked to serum concentrations and medication exposure. Linear mixed-effects models with random intercepts and slopes assessed predictors of weight trajectories, with fixed effects including age, sex, baseline weight, norclozapine concentration, opioid agonist therapy (OAT), augmenting antipsychotic defined daily dose, and adjunctive metformin and aripiprazole. Interaction terms between time and adjunctive agents evaluated effects on weight trajectories.ResultsEighty individuals contributed 306 matched serum concentration-weight observations. The cohort was predominantly male with schizophrenia and comorbid SUDs. Higher baseline weight and greater time between admission and blood draw were associated with increased weight. In adjusted models, norclozapine concentration and OAT were associated with higher weight. Metformin was associated with attenuation of weight gain over time (time × metformin: B = -2.63, 95% CI -4.49 to -0.76), whereas aripiprazole was not (B = -0.38, 95% CI -2.58 to 1.82).ConclusionMetformin was associated with attenuation of weight gain trajectory in this population, whereas aripiprazole showed no clear effect. These findings highlight substantial metabolic vulnerability in inpatient concurrent disorders settings and support early preventive metabolic interventions during clozapine treatment.