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

Siskind, Dan J., Leung, Janni, Russell, Anthony W., Wysoczanski, Daniel and Kisely, Steve (2016) Metformin for clozapine associated obesity: a systematic review and meta-analysis. PLoS ONE, 11 6: . doi:10.1371/journal.pone.0156208

Author Siskind, Dan J.
Leung, Janni
Russell, Anthony W.
Wysoczanski, Daniel
Kisely, Steve
Title Metformin for clozapine associated obesity: a systematic review and meta-analysis
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-06-15
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0156208
Open Access Status DOI
Volume 11
Issue 6
Total pages 15
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2017
Language eng
Formatted 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
Keyword Obesity
Glucagon-like peptide (GLP-1)
Weight loss
Clozapine associated weight gain
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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