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

Abstract

AimsSchizophrenia 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 methodsAntipsychotic‐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.ResultsBetween 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.ConclusionsTreatment 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.

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

“…These corrected results correspond to the second paragraph Section 3.2 in the original paper . Changes are shown in italic font.…”

“…“Treatment of antipsychotic‐associated obesity with a GLP‐1 receptor agonist (GLP‐1RA): The TAO trial” was the first clinical investigation of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment (exenatide 2 mg once‐weekly or placebo) in antipsychotic‐treated schizophrenia patients with obesity . Recently, we published the main results from the TAO trial as an original article in Diabetes, Obesity and Metabolism …”

“…The error specifically relates to our secondary analyses of the metabolic blood markers. In these analyses, the coding of “visit type” had been shuffled, and in turn, the data and statistical tests of the metabolic blood markers in Section 2.6.4 and Table were based on incorrect visit types . Reductions in body weight are typically associated with improvement in metabolic blood markers, and our unexpected report of a post ‐intervention worsening of blood metabolic variables after 3 months, was therefore incorrect and misleading.…”

Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

“…One study was restricted to participants receiving clozapine and olanzapine, and another to clozapine alone . The third study included a naturalistic patient sample treated with clozapine, olanzapine, aripiprazole, risperidone, paliperidone, quetiapine, ziprasidone, amisulpride and sertindole . After initial publication, an erratum on corrected metabolic blood markers was published for the third study, and these data were used in the current meta‐analysis .…”

Treatment of clozapine‐associated obesity and diabetes with exenatide in adults with schizophrenia: A randomized controlled trial (CODEX)

“…Exenatide may have advantages over daily liraglutide in that it is a once‐weekly injection, increasing the chance of adherence in people on clozapine, especially if they gain confidence in their ability to self‐administer. One trial of weekly exenatide for obese people with schizophrenia showed equivocal results, but that study only ran for 12 weeks and did not limit participants to those on olanzapine or clozapine, the medications most likely to affect the GLP‐1 pathway …”