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Meta-Analysis
. 2016 Jun 15;11(6):e0156208.
doi: 10.1371/journal.pone.0156208. eCollection 2016.

Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis

Dan J Siskind  1   2   3 , Janni Leung  3   4 , Anthony W Russell  1   5 , Daniel Wysoczanski  1   2 , Steve Kisely  1   2   6   7
Affiliations
Meta-Analysis

Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis

Dan J Siskind et al. PLoS One. .

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA Flow Diagram.
Fig 2
Fig 2. Forest Plot of Weight, BMI and Waist Circumference*.
*weight = body weight in kg; BMI = Body Mass Index in kg/m2; Waist = waist circumference in cm.
Fig 3
Fig 3. Forest Plot of Metabolic Syndrome Components (excluding Waist Circumference).
HDL = High Density Lipoprotein; Systolic = Systolic Blood Pressure (in mmHg); Diastolic = Diastolic Blood Pressure (in mmHg).
Fig 4
Fig 4. Forest Plot of LDL, Insulin and HOMA*.
* LDL = Low Density Lipoprotein; HOMA = Homeostatic Model Assessment.
See this image and copyright information in PMC

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MeSH terms