The Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (The METS Study)

Inclusion Criteria: * Outpatients with a diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID) * Duration of illness greater than 1 year, as defined by having initiated antipsychotic treatment at least 1 year prior to study entry * Adequate decisional capacity to make a choice about participating in this research study * Body mass index (BMI) at or greater than 27 * Currently being treated with one or a combination of two antipsychotic medications (typical or atypical) and on that drug regimen for at least 2 months prior to study entry, with stable dosages for at least 1 month * If taking antidepressants, mood stabilizers, or anxiolytics, the dose must be stable for at least 1 month prior to study entry * Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices or barrier methods such as condoms; and diaphragms and spermicides. Exclusion Criteria: * Inpatient status * Clinical Global Impression Severity (CGI-S) score greater than 6 * Currently being treated with more than two antipsychotic medications * Fasting glucose greater than 125 * Diagnosis of diabetes mellitus or treatment with insulin or oral hypoglycemics * Previous or current treatment with metformin * Diagnosis of congestive heart failure * Renal impairment, as defined by a serum creatinine level greater than 1.5 in males or greater than 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits * Hepatic disease, as defined by aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) greater than 1.5 times upper limit of normal (ULN), or total bilirubin greater than 1.2 times ULN * Metabolic acidosis, as defined by serum carbon dioxide less than the lower limit of normal * Known hypersensitivity to metformin * Pregnant or breastfeeding * Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material * Alcohol abuse or dependence within the past month, as determined by the SCID * Other serious and unstable medical condition in the judgment of the investigator * Diagnosis of mental retardation, delirium, or dementia, as defined by DSM-IV-TR * Failed to discontinue 4 weeks prior to study entry any medication used for weight loss * Concurrent treatment with certain drugs that are known to increase metformin blood levels should be discussed with the Project Medical Officer.