T44. 12-MONTH FOLLOW UP OF METABOLIC MEASURES FOLLOWING A RANDOMISED CONTROLLED TRIAL OF TREATMENT OF CLOZAPINE ASSOCIATED OBESITY AND DIABETES WITH EXENATIDE (CODEX)

Abstract

Background: Clozapine is associated with high rates of obesity and type 2 diabetes (T2DM). Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, can counter clozapine-associated GLP-1 dysregulation. Our randomized, controlled (RCT), open-label, pilot trial of once-weekly extended-release subcutaneous exenatide or treatment as usual (TAU) for 24 weeks (n=28), found 6/14 people on exenatide achieved >5% weight loss vs 1/14 receiving usual care (P = .029). Compared with TAU, participants on exenatide had greater mean weight loss body mass index (BMI) reduction, and reduced fasting glucose and glycated haemoglobin (HbA1c) levels. Methods: We followed up CODEX trial participants at 12 months following the end of the trial. We collected information on weight, BMI, waist circumference, blood pressure, fasting glucose, HbA1c, and use of metformin. The primary outcome of interest was change in weight. Change in these parameters from trial baseline to 12 months post endpoint and trial endpoint to 12 months post endpoint was compared between those formerly in the exenatide and TAU arms. Results: There were no significant differences between baseline and 12-months post endpoint for any of the variables. Data from endpoint to 12-month follow up point showed significantly greater increases among the former exenatide group compared to the former TAU group for weight, BMI, and proportion with >5% weight gain. Stratifying the dataset by whether participants were on metformin six months after the end of the trial did not alter the overall results. Discussion: There were significant increases in weight and BMI in the 12 months post endpoint for the former exenatide group, however there were no significant differences in weight and BMI between baseline and 12-month post endpoint. This is in keeping with other GLP-1RA studies. This information suggests the need for continued use of exenatide among people on clozapine who have achieved weight loss.