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


BACKGROUND
PROSPERO registration number: CRD42015029723.
School of Medicine, The University of Queensland, Brisbane, Qld, Australia.|Metro South Addiction and Mental Health Service, Brisbane, Qld, Australia.|QCMHR, School of Public Health, The University of Queensland, Brisbane, Qld, Australia.
Dan J
http://orcid.org/0000-0002-2072-9216
DJ
Siskind
QCMHR, School of Public Health, The University of Queensland, Brisbane, Qld, Australia.|Institute for Health Metrics and Evaluation, University of Washington, Seattle, United States of America.
Janni
J
Leung
School of Medicine, The University of Queensland, Brisbane, Qld, Australia.|Department of Endocrinology, Princess Alexandra Hospital, Brisbane, Qld, Australia.
Anthony W
AW
Russell
School of Medicine, The University of Queensland, Brisbane, Qld, Australia.|Metro South Addiction and Mental Health Service, Brisbane, Qld, Australia.
Daniel
D
Wysoczanski
School of Medicine, The University of Queensland, Brisbane, Qld, Australia.|Metro South Addiction and Mental Health Service, Brisbane, Qld, Australia.|Griffith Institute of Health, Griffith University, Brisbane, Qld, Australia.|Departments of Psychiatry, Community Health and Epidemiology, Dalhousie University, Halifax, Canada.
Steve
S
Kisely
D014150:Antipsychotic Agents / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003024:Clozapine / Q000009:adverse effects; D005215:Fasting / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000097:blood / Q000517:prevention & control; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014280:Triglycerides; D008687:Metformin; D003024:Clozapine