Pharmacopsychiatry 2019; 52(01): 24-31
DOI: 10.1055/s-0044-101466
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials

Wei Zheng*
1  The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
Qing-E Zhang*
2  The National Clinical Research Center for Mental Disorders, China & Center of Depression, Beijing Institute for Brain Disorders & Mood Disorders Center, Beijing Anding Hospital, Capital Medical University, Beijing, China
Dong-Bin Cai
3  Clinics of Chinese Medicine, First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
Xin-Hu Yang
1  The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
Gabor S. Ungvari
4  The University of Notre Dame Australia / Graylands Hospital, Perth, Australia
Chee H. Ng
5  Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
Ren-Rong Wu
6  Mental Health Institute of the Second Xiangya Hospital & National Technology Institute of Psychiatry & Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, China
Yu-Tao Xiang
7  Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China
› Author Affiliations
Further Information

Publication History

received 11 July 2017
revised 25 November 2017

accepted 16 January 2018

Publication Date:
27 February 2018 (online)


Introduction Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia.

Methods Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals.

Results Six RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods.

Conclusion Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.

Review registration: CRD42017059198

* These authors contributed equally to this work.

Supporting Information