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Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment: Meta-Analysis of Randomized Placebo-Controlled Trials

Zheng, Wei MD*; Li, Xian-Bin MD†‡; Tang, Yi-Lang MD, PhD†§; Xiang, Ying-Qiang MD, PhD; Wang, Chuan-Yue MD, PhD†‡; de Leon, Jose MD∥¶#

Journal of Clinical Psychopharmacology: October 2015 - Volume 35 - Issue 5 - p 499–509
doi: 10.1097/JCP.0000000000000392
Original Contributions

This meta-analysis examined the effectiveness and safety of metformin to prevent or treat weight gain and metabolic abnormalities associated with antipsychotic drugs. We systematically searched in both English- and Chinese-language databases for metformin randomized controlled clinical trials (RCTs) using placebo in patients taking antipsychotics. Twenty-one RCTs (11 published in English and 10 in Chinese) involving 1547 subjects (778 on metformin, 769 on placebo) were included in this meta-analysis. Metformin was significantly superior to placebo (standard mean differences, −0.69 to −0.51; P = 0.01–0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol). Metformin was significantly superior to placebo in some secondary outcome measures but not in others. Significantly higher frequencies of nausea/vomiting and diarrhea were found in the metformin group, but no differences were found in other adverse drug reactions. In the metformin group, the frequency of nausea/vomiting was 14%, and of diarrhea, 7%. Subgroup and sensitivity analyses demonstrated that primary outcomes were influenced by ethnicity, treatment style (intervention vs prevention), metformin dose, study duration, and mean age. Body weight standard mean difference was −0.91 (confidence interval [CI], −1.40 to −0.41) in 3 prevention RCTs in naive patients, −0.66 (CI, −1.02 to −0.30) in 5 intervention RCTs during the first year, and −0.50 (CI, −0.73 to −0.27) in 9 intervention RCTs in chronic patients. This meta-analysis suggests that adjunctive metformin is an effective, safe, and reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities.

Supplemental digital content is available in the text.

From the *Guangzhou Brain Hospital (Guangzhou Huiai Hospital), Affiliated Hospital of Guangzhou Medical University, Guangzhou; †Beijing Key Laboratory of Mental Disorders, Department of Psychiatry, Beijing Anding Hospital, Capital Medical University; and ‡Center of Schizophrenia, Beijing Institute for Brain Disorders, Laboratory of Brain Disorders (Capital Medical University), Ministry of Science and Technology, Beijing, China; §Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA; ∥University of Kentucky, Mental Health Research Center at Eastern State Hospital, Lexington, KY; ¶Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada; and #Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apóstol Hospital, University of the Basque Country, Vitoria, Spain.

Received March 1, 2015; accepted after revision July 3, 2015.

Reprints: Chuan-Yue Wang, MD, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Ave, Xicheng District, Beijing 100088, China (e-mail:

No commercial organizations had any role in the completion or publication of this study. This article was completed without any external funding. Drs Zheng, Li, Xiang, Wang, and de Leon declare no competing interest during the last 36 months. During the last 36 months, Dr Tang received a pilot research grant from Janssen Pharmaceuticals, Inc, and payment for writing or reviewing manuscripts from the American Physician Institute, Inc.

Drs Zheng and Li contributed equally to the article review, statistical analyses, and writing of the first draft. Dr Xiang assisted in the study selection and improvement of all drafts. Drs Tang and Wang contributed to the improvement of all drafts. Dr de Leon provided statistical suggestions and rewrote the article to accommodate the journal's style. All the authors contributed to the interpretation of data and approved the final manuscript.

Metformin is not approved by the Food and Drug Administration for the treatment of weight gain and metabolic abnormalities associated with antipsychotic treatment.

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