D Siskind, AW Russell, C Gamble, K Winckel, K Mayfield, S Hollingworth, I Hickman, V Siskind and S Kisely,
Diabetes, obesity & metabolism, Nov 30 2017
Clozapine causes obesity and type-2 diabetes (T2DM). Glucagon-like-peptide-1 (GLP-1) agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomised, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. Twenty-eight outpatients were randomised to once-weekly extended-release sub-cutaneous exenatide or usual care for 24 weeks. The primary outcome was proportion with >5% weight loss. All 28 participants completed the study: 3/14 in the exenatide group and 2/14 in the usual care had T2DM. Six people on exenatide achieved >5% weight loss versus one usual care (p=0.029). Compared to usual care, participants on exenatide had greater mean weight loss (-5.29kg vs -1.12kg, p=0.015), BMI reduction (-1.78 vs -0.39 p=0.019), and reduced fasting glucose (-0.34 vs 0.39, p=0.036) and HbA1c (-0.21 vs 0.03, p=0.004). There were no significant differences in other metabolic syndrome components. Exenatide may be a promising therapeutic agent for glycaemic control and weight loss in clozapine-treated people with obesity, and could assist in reducing clozapine-associated cardio-metabolic morbidity and mortality.