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JAMA Psychiatry. 2017 Jul 1;74(7):719-728. doi: 10.1001/jamapsychiatry.2017.1220.

Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder: A Randomized Clinical Trial.

Author information

1
Psychiatric Centre, University of Copenhagen, Copenhagen, Denmark2currently with Novo Nordisk A/S, Bagsværd, Denmark.
2
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
3
Psychiatric Centre, University of Copenhagen, Copenhagen, Denmark.
4
Department of Psychiatry, Aalborg University Hospital, Aalborg University, Aalborg, Denmark.
5
Department of Clinical Physiology, Nuclear Medicine and PET, Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
6
Novo Nordisk Foundation Center for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark7Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
7
Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
8
Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York10Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, New York11Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York12Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York.
9
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark13Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
10
Psychiatric Centre, University of Copenhagen, Copenhagen, Denmark13Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark14Steno Diabetes Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.

Abstract

Importance:

Compared with the general population, patients with schizophrenia have a 2- to 3-fold higher mortality rate primarily caused by cardiovascular disease. Previous interventions designed to counteract antipsychotic-induced weight gain and cardiometabolic disturbances reported limited effects.

Objectives:

To determine the effects of the glucagon-like peptide-1 receptor agonist liraglutide added to clozapine or olanzapine treatment of schizophrenia spectrum disorders.

Design, Setting, and Participants:

This randomized clinical double-blind trial enrolled participants at 2 clinical sites in Denmark. Of 214 eligible participants with a schizophrenia spectrum disorder, 103 were randomized to liraglutide or placebo. Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and had prediabetes. Data were collected from May 1, 2013, through February 25, 2016.

Interventions:

Treatment for 16 weeks with once-daily subcutaneous injection of liraglutide or placebo. Trial drug therapy was titrated during the first 2 weeks of the study.

Main Outcomes and Measures:

The primary end point was change in glucose tolerance estimated by a 75-g oral glucose tolerance test result. Secondary end points included change in body weight and cardiometabolic parameters.

Results:

Of the 103 patients undergoing randomization (60 men [58.3%] and 43 women [41.7%]), 97 were included in the efficacy analysis, with a mean (SD) age of 42.5 (10.5) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 33.8 (5.9). The liraglutide and placebo groups had comparable characteristics (mean [SD] age, 42.1 [10.7] vs 43.0 [10.5] years; 30 men in each group; mean [SD] body mass index, 33.7 [5.1] vs 33.9 [6.6]). A total of 96 randomized participants (93.2%) completed the trial. Glucose tolerance improved in the liraglutide group compared with the placebo group (P < .001). Altogether, 30 liraglutide-treated participants (63.8%) developed normal glucose tolerance compared with 8 placebo-treated participants (16.0%) (P < .001; number needed to treat, 2). Body weight decreased with liraglutide compared with placebo (-5.3 kg; 95% CI, -7.0 to -3.7 kg). Reductions in waist circumference (-4.1 cm; 95% CI, -6.0 to -2.3 cm), systolic blood pressure (-4.9 mm Hg; 95% CI, -9.5 to -0.3 mm Hg), visceral fat (-250.19 g; 95% CI, -459.9 to -40.5 g), and low-density lipoprotein levels (-15.4 mg/dL; 95% CI, -23.2 to -7.7 mg/dL) occurred with liraglutide compared with placebo. Adverse events with liraglutide affected mainly the gastrointestinal tract.

Conclusions and Relevance:

Liraglutide significantly improved glucose tolerance, body weight, and cardiometabolic disturbances in patients with schizophrenia spectrum disorders treated with clozapine or olanzapine.

Trial Registration:

clinicaltrials.gov Identifier: NCT01845259.

PMID:
28601891
PMCID:
PMC5710254
DOI:
10.1001/jamapsychiatry.2017.1220
[Indexed for MEDLINE]
Free PMC Article

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