Effect of GLP-1 receptor agonists on obesity in patients with severe mental illness: A state hospital case series of clozapine-treated patients

Abstract

Patients with severe mental illness (SMI) are ∼3 times more likely to live with obesity and experience a 2 - 3 fold higher mortality rate from cardiovascular disease compared to the non-psychiatric general population. Antipsychotic drugs (APDs), though effective in ameliorating symptoms of SMI, directly contribute to adverse metabolic effects including weight gain. Counteracting antipsychotic induced weight gain (AIWG) with pharmacological strategies and lifestyle modifications has demonstrated limited effects in previous studies. The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has recently become widespread in medicine. GLP-1 RAs offer a relatively novel and potentially effective approach to counteract weight gain and improve cardiometabolic abnormalities associated with commonly prescribed APDs in individuals with SMI.

In this retrospective case series, two chronic state mental health hospital patients living with obesity in the context of past medical issues and currently receiving clozapine, an APD with high metabolic risks, had also been receiving dulaglutide (supplemented with diet and weight management counsel) as an off-label intervention to promote weight loss. Retrospective review of patient data revealed encouraging results on weight and glyco-metabolic parameters in each of the two cases. In particular, in weight, Patient 1 achieved a 22 % reduction and Patient 2 achieved a 16 % reduction. In HbA1c levels, both patients achieved a 5 % reduction. In triglyceride levels, Patient 1 achieved a 46 % reduction and Patient 2 achieved a 68 % reduction. These results provide a compelling argument for the adoption of GLP-1 RAs in treatment plans for such oft-forgotten and stigmatized state mental health hospital patients, who often: have chronic lengths of stay, are on clozapine and/or polypharmacy medication regimens, are sedentary, and have AIWG, metabolic syndrome, or other significant comorbidities.