Metformin for clozapine associated obesity: a systematic review and meta-analysis

Siskind, Dan J.; Leung, Janni; Russell, Anthony W.; Wysoczanski, Daniel; Kisely, Steve

doi:10.1371/journal.pone.0156208

Cited by 123Schizophrenia research and treatmentPharmacology and Obesity TreatmentDiabetes Treatment and Management

Metformin for clozapine associated obesity: a systematic review and meta-analysis

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Siskind, Dan J., Leung, Janni, Russell, Anthony W., Wysoczanski, Daniel, Kisely, Steve·2016·PLoS ONE

DOI 10.1371/journal.pone.0156208PMC PMC4909277

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Abstract

BACKGROUND: Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. METHODS: We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. RESULTS: Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. CONCLUSIONS: Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. TRIAL REGISTRATION: PROSPERO registration number: CRD42015029723.

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Improving fitness may offer a similarly motivating but more achievable goal for exercise interventions in people with mental illness.
“Improving fitness may offer a similarly-motivating 271 , but more achievable, 279,280 goal for exercise interventions in people with mental illness.”
From The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness (2019) · cites this paper as [280]

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Siskind, D. J., Russell, A. W., Suetani, S., Flaws, D., Kisely, S. R., Moudgil, V., Northwood, K. S., Robinson, G., Scott, J. G., STEDMAN, T. J., et al. (2021) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253211045248 · Cited by 10 · see citing works
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Authors: Siskind, D. J., Leung, J., Russell, A. W., Wysoczanski, D., & Kisely, S.
Affiliations: The University of Queensland (AU)
Griffith University (AU)
Corresponding author: Siskind, Dan J.
ORCID: Siskind, Dan J.
Leung, Janni
Russell, Anthony W.
Kisely, Steve
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2016-06-15
Volume: 11
Issue: 6
Pages: e0156208
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0156208
PMC: PMC4909277
OpenAlex: W2436128242
Cited by: 122
References: 32
Citations by year: 2026: 7 · 2025: 13 · 2024: 10 · 2023: 9 · 2022: 15 · 2021: 22 · 2020: 14 · 2019: 10 · 2018: 12 · 2017: 7 · 2016: 3
FWCI: 1.53
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Griffith Research Online (submittedVersion, cc-by)
Funders: University of Queensland
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: metformin, clozapine, obesity, metabolic syndrome, weight loss, glucagon-like peptide-1, antipsychotic adverse effects, treatment-resistant schizophrenia, body mass index, waist circumference, fasting blood glucose, triglycerides
MeSH terms: Blood Glucose, Body Weight, Clozapine, Fasting, Humans, Hypoglycemic Agents, Metformin, Obesity, Schizophrenia, Antipsychotic Agents, Triglycerides, Weight Gain, Body Mass Index, Randomized Controlled Trials as Topic, Treatment Outcome, Metabolic Syndrome, Waist Circumference

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Metformin for clozapine associated obesity: a systematic review and meta-analysis

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