Effect of GLP‐1 receptor agonist treatment on body weight in obese antipsychotic‐treated patients with schizophrenia: a randomized, placebo‐controlled trial

• Published in: Diabetes, obesity & metabolism Vol. 19; no. 2; pp. 162 - 171
• Main Authors: Ishøy, Pelle L., Knop, Filip K., Broberg, Brian V., Bak, Nikolaj, Andersen, Ulrik B., Jørgensen, Niklas R., Holst, Jens J., Glenthøj, Birte Y., Ebdrup, Bjørn H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2017; Wiley Subscription Services, Inc
• Subjects: Absorptiometry, Photon; Adult; antidiabetic drug; Antipsychotic Agents - therapeutic use; Antipsychotics; Blood Glucose - metabolism; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Composition; Body Weight; Diabetes; Double-Blind Method; Evidence-based medicine; Exenatide; Female; GLP‐1 analogue; Glucagon-Like Peptide-1 Receptor - agonists; Glycated Hemoglobin A - metabolism; Humans; Incretins - therapeutic use; Male; Metabolism; Middle Aged; Obesity; Obesity - complications; Obesity - drug therapy; Original; Patients; Peptides - therapeutic use; Psychotropic drugs; randomized trial schizophrenia; Schizophrenia; Schizophrenia - complications; Schizophrenia - drug therapy; Treatment Outcome; Venoms - therapeutic use; Waist Circumference; Waist-Hip Ratio; Weight control; Weight Loss; Young Adult; antidiabetic drug; GLP-1 analogue; randomized trial schizophrenia; exenatide
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12795

Aims Schizophrenia is associated with cardiovascular co‐morbidity and a reduced life‐expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP‐1RA, exenatide once‐weekly, in non‐diabetic, antipsychotic‐treated, obese patients with schizophrenia. Material and methods Antipsychotic‐treated, obese, non‐diabetic, 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 loss of body weight after treatment and repeated measures analysis of variance was used as statistical analysis. Results Between March 2013 and June 2015, 40 patients completed the trial. At baseline, 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). The exenatide and placebo groups experienced significant ( P = .004), however similar ( P = .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment. Conclusions Treatment with exenatide once‐weekly did not promote weight loss in obese, antipsychotic‐treated patients with schizophrenia compared to placebo. Our results could suggest that the body weight‐lowering effect of GLP‐1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, anti‐obesity regimens effective in the general population may not be readily implemented in antipsychotic‐treated patients with schizophrenia.