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

• Published in: PloS one 2016-06, Vol.11 (6), p.e0156208-e0156208
• Main Authors: Siskind, Dan J, Leung, Janni, Russell, Anthony W, Wysoczanski, Daniel, Kisely, Steve
• Format: Article
• Language: English
• Subjects: Addictions; Antidiabetics; Antipsychotic Agents - adverse effects; Antipsychotics; Bibliographic data bases; Biology and Life Sciences; Blood Glucose - metabolism; Blood pressure; Body mass; Body Mass Index; Body Weight - drug effects; Body weight loss; Clinical trials; Clozapine; Clozapine - adverse effects; Diabetes; Diabetes mellitus; Fasting; Fasting - blood; Glucagon; Glucose; Health services; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Intervention; Lipoproteins; Medicine; Medicine and Health Sciences; Mental disorders; Mental health; Meta-analysis; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - prevention & control; Metformin; Metformin - therapeutic use; Obesity; Obesity - chemically induced; Obesity - drug therapy; Peptides; Physical Sciences; Psychiatry; Psychotropic drugs; Public health; Randomized Controlled Trials as Topic; Research and Analysis Methods; Schizophrenia; Schizophrenia - drug therapy; Sensitivity analysis; Studies; Systematic review; Treatment Outcome; Triglycerides; Triglycerides - blood; Waist Circumference - drug effects; Weight control; Weight Gain - drug effects; Weight loss; Weight reduction
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156208

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. 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. 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. 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. PROSPERO registration number: CRD42015029723.