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

National Institutes of Health (NIH)

Status and phase

Completed

Phase 4

Conditions

Schizophrenia

Treatments

Drug: Metformin

Drug: Placebo

Study type

Interventional

Funder types

NIH

Identifiers

NCT00816907

N01MH90001 DSIR AT (Other Identifier)

N01 MH090001-03

Details and patient eligibility

About

This study will test the usefulness of the medication metformin in treating people with schizophrenia or schizoaffective disorder who are overweight and also taking antipsychotic medications.

Full description

Schizophrenia is a chronic mental disorder that is characterized, in part, by psychotic symptoms. Psychotic symptoms include hallucinations and delusions, in which a person has abnormal experiences or beliefs, and are commonly treated with antipsychotic medications. Unfortunately, a side effect of many antipsychotics is unwanted weight gain, which can lead to physical illness. Use of the drug metformin has resulted in weight loss among diabetics. Metformin has also been shown to cause weight loss in preliminary studies of people taking atypical antipsychotics-a newer, second generation of antipsychotic medications. Metformin is currently approved by the Food and Drug Administration to treat only people with diabetes. This study will test the usefulness of prescribing metformin as a second medication to treat people with schizophrenia or schizoaffective disorder who are overweight and taking antipsychotics. The study will also provide important feasibility information for future larger studies.

Participation in this study will last 16 weeks. After undergoing baseline assessments, participants will be randomly assigned to receive either metformin or placebo, both of which will be taken twice daily for the duration of the study. All participants will also receive behavioral therapy that will teach them about reducing their weight through diet and exercise. Participants will undergo assessments at 11 study visits: the first 2 will include screening and baseline testing, the next 2 visits will take place after the first and second weeks of receiving treatment, and the last 7 visits will take place every 2 weeks until the end of the study. Assessments will include measurements of body weight, waist-to-hip ratio, and vital signs; clinical interviews about medication adherence, side effects, and alcohol use; and monthly blood tests to assess levels of lipids, glucose, insulin, and hemoglobin A1c.

Enrollment

146 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.