SU18. GLP-1 Receptor Agonist Treatment in Schizophrenia Patients With Obesity

ABSTRACT: Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes, and we investigated metabolic and cognitive effects of the GLP-1RA, exenatide once weekly, in nondiabetic, antipsychotic-treated, obese patients with schizophrenia. Methods: In this investigator-initiated trial, antipsychotic-treated, obese, nondiabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for 3 months. The primary outcome was body weight loss after treatment. Secondary endpoints comprised blood pressure, biochemistry, measurements of body composition, and cognition. Results: Forty patients completed the trial. At baseline, the mean body weight was 118.3?±?16.0?kg in the exenatide group and 111.7?±?18.0?kg in the placebo group, with no group differences (P = .23). After 3 months of treatment, the exenatide and placebo groups experienced significant (P = .004), but, similar (P = .98) weight losses of 2.24?±?3.3?kg and 2.23?±?4.4?kg, respectively. The exenatide group had a significant decrease in central 24-h systolic blood pressure of 6.8?mm/Hg (P = .004) and a decrease in the pulse wave velocity (a measure of arterial stiffness) of 0.3 m/s (P = .007). Changes in biochemistry, body composition, and cognition were similar in the groups (P < .47). Exenatide once weekly was well tolerated. Conclusion: Treatment with exenatide once weekly did not promote weight loss in obese, antipsychotic-treated patients with schizophrenia compared to placebo. This suggests that the body weight-lowering effect of GLP-1RAs involves dopaminergic signaling and implies that antiobesity regimens effective in the general population may not be readily implemented in antipsychotic-treated patients with schizophrenia. ClinicalTrials.gov identifier: NCT01794429.

SUBMITTER: Ishøy P 

PROVIDER: S-EPMC5476046 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature