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

Pelle L Ishøy, Filip K Knop, Brian V Broberg, Nikolaj Bak, Ulrik B Andersen, Niklas Rye Jørgensen, Jens J Holst, Birte Y Glenthøj, Bjørn H Ebdrup

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Resumé

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.

OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism
Vol/bind19
Udgave nummer2
Sider (fra-til)162–171
ISSN1462-8902
DOI
StatusUdgivet - 2017

Fingeraftryk

Randomized Controlled Trials
Placebos
Dopamine Agonists
Life Expectancy
Type 2 Diabetes Mellitus
Glucagon-Like Peptide-1 Receptor
exenatide
Pharmaceutical Preparations
Population

Citer dette

Ishøy, Pelle L ; Knop, Filip K ; Broberg, Brian V ; Bak, Nikolaj ; Andersen, Ulrik B ; Rye Jørgensen, Niklas ; Holst, Jens J ; Glenthøj, Birte Y ; Ebdrup, Bjørn H. / Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia : a randomized, placebo-controlled trial. I: Diabetes, Obesity and Metabolism. 2017 ; Bind 19, Nr. 2. s. 162–171.
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title = "Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia: a randomized, placebo-controlled trial",
abstract = "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.",
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language = "English",
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journal = "Diabetes, Obesity and Metabolism",
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Ishøy, PL, Knop, FK, Broberg, BV, Bak, N, Andersen, UB, Rye Jørgensen, N, Holst, JJ, Glenthøj, BY & Ebdrup, BH 2017, 'Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia: a randomized, placebo-controlled trial', Diabetes, Obesity and Metabolism, bind 19, nr. 2, s. 162–171. https://doi.org/10.1111/dom.12795

Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia : a randomized, placebo-controlled trial. / Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V; Bak, Nikolaj; Andersen, Ulrik B; Rye Jørgensen, Niklas ; Holst, Jens J; Glenthøj, Birte Y; Ebdrup, Bjørn H.

I: Diabetes, Obesity and Metabolism, Bind 19, Nr. 2, 2017, s. 162–171.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

AU - Ishøy, Pelle L

AU - Knop, Filip K

AU - Broberg, Brian V

AU - Bak, Nikolaj

AU - Andersen, Ulrik B

AU - Rye Jørgensen, Niklas

AU - Holst, Jens J

AU - Glenthøj, Birte Y

AU - Ebdrup, Bjørn H

N1 - © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

PY - 2017

Y1 - 2017

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 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.

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 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.

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 -