Dan Siskind1,2, Margaret Hahn3,4, Christoph U Correll5,6,7, Anders Fink-Jensen8,9, Anthony W Russell2,10, Nikolaj Bak11, Brian V Broberg11, Julie Larsen8,12, Pelle L Ishøy11, Tina Vilsbøll9,13, Filip K Knop9,13,14, Steve Kisely1,2, Bjørn H Ebdrup9,11. 1. Metro South Addiction and Mental Health Service, Brisbane, Australia. 2. School of Medicine, University of Queensland, Brisbane, Australia. 3. Centre for Addiction and Mental Health, Toronto, Canada. 4. Department of Psychiatry, University of Toronto, Toronto, Canada. 5. Department of Psychiatry, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, New York. 6. Hofstra Northwell School of Medicine, Department of Psychiatry and Molecular Medicine, Hempstead, New York. 7. Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. 8. Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services - Capital Region of Denmark, Copenhagen, Denmark. 9. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 10. Department of Endocrinology, Princess Alexandra Hospital, Brisbane, Australia. 11. Centre for Neuropsychiatric Schizophrenia Research & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Copenhagen, Denmark. 12. Novo Nordisk A/S, Research and Development, Søborg, Denmark. 13. Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 14. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
AIMS: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls. MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP-1RA)'. Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent. RESULTS: Three studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly impact outcomes. Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001). Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8). CONCLUSION: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.
AIMS: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls. MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP-1RA)'. Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent. RESULTS: Three studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly impact outcomes. Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001). Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8). CONCLUSION: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.
Authors: C U Correll; Ofer Agid; Benedicto Crespo-Facorro; Andrea de Bartolomeis; Andrea Fagiolini; Niko Seppälä; Oliver D Howes Journal: CNS Drugs Date: 2022-06-27 Impact factor: 6.497
Authors: Davy Vancampfort; Joseph Firth; Christoph U Correll; Marco Solmi; Dan Siskind; Marc De Hert; Rebekah Carney; Ai Koyanagi; André F Carvalho; Fiona Gaughran; Brendon Stubbs Journal: World Psychiatry Date: 2019-02 Impact factor: 49.548
Authors: Dan Siskind; Erin Gallagher; Karl Winckel; Samantha Hollingworth; Steve Kisely; Joseph Firth; Christoph U Correll; Wade Marteene Journal: Schizophr Bull Date: 2021-07-08 Impact factor: 9.306