TY - JOUR

T1 - Effect of GLP-1 Receptor Agonist Treatment on Body weight in Obese Antipsychotic-treated Patients with Schizophrenia

T2 - a Randomized, Placebo-controlled Trial Byline

AU - Ishøy, Pelle L

AU - Knop, Filip K

AU - Broberg, Brian V

AU - Bak, Nikolaj

AU - Andersen, Ulrik B

AU - Jørgensen, Niklas R

AU - Holst, Jens J

AU - Glenthøj, Birte Y

AU - Ebdrup, Bjørn H

N1 - This article is protected by copyright. All rights reserved.

PY - 2017/2

Y1 - 2017/2

N2 - 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 the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like 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 three months. The primary outcome was body weight loss 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, 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 = 0.23). The exenatide and placebo groups experienced significant (P = 0.004), however, similar (P = 0.98) weight losses of 2.24 ± 3.3 kg and 2.23 ± 4.4 kg, respectively, after three 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 ClinicalTrials.gov identifier: NCT01794429.

AB - 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 the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like 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 three months. The primary outcome was body weight loss 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, 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 = 0.23). The exenatide and placebo groups experienced significant (P = 0.004), however, similar (P = 0.98) weight losses of 2.24 ± 3.3 kg and 2.23 ± 4.4 kg, respectively, after three 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 ClinicalTrials.gov identifier: NCT01794429.

UR - https://doi.org/10.1111/dom.13204

U2 - 10.1111/dom.12795

DO - 10.1111/dom.12795

M3 - Journal article

C2 - 27717222

VL - 19

SP - 162

EP - 171

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 2

ER -