The Effect of Metformin on Anthropometrics and Insulin Resistance in Patients Receiving Atypical Antipsychotic Agents: A Meta-Analysis

Context: In the Clinical Antipsychotic Trials of Intervention Effectiveness, atypical antipsychotics (AAPs) were found to be associated with weight gain and impairment of glucose metabolism. While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance.

Objective: To characterize metformin’s impact on anthropometrics and insulin resistance in patients taking AAPs.

Data sources: A systematic literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was conducted from the earliest possible date through December 31, 2008. The search was performed using the following Medical Subject Headings and text keywords: metformin, biguanide(s), in combination with neuroleptic(s), neuroleptic drug(s), antipsychotic(s), dopamine antagonist(s), atypical antipsychotic(s), psychotropic(s), risperidone, olanzapine, quetiapine, ziprasidone, sulpiride, clozapine, iloperidone, aripiprazole, paliperidone, melperone, bifeprunox, amisulpride, zotepine, and sertindole.

Study selection: Six of 62 identified studies (N=336 participants) met our inclusion criteria: randomized, placebo-controlled trials of metformin in patients taking AAPs with data on weight, body mass index (BMI), waist circumference, insulin resistance (determined using the homeostasis model assessment of insulin resistance [HOMA-IR]), and/or a diagnosis of diabetes.

Data extraction: Data were independently abstracted by 2 investigators; disagreements were resolved through discussion or by a third investigator using a standardized data abstraction tool. For continuous endpoints, the weighted mean difference (WMD) of the change from baseline with 95% CI was calculated as the difference between the mean in the metformin and placebo groups. For categorical endpoints, the pooled relative risk (RR) with 95% CI was calculated. A random-effects model was used for all analyses.

Data synthesis: Compared to placebo, the metformin group had significantly reduced weight (WMD, 3.16 kg; P=.0002), BMI (WMD, 1.21 kg/m2; P=.0001), waist circumference (WMD, 1.99 cm; P=.005), and HOMA-IR (WMD, 1.71; P=.004). The reduction in risk of diabetes was not statistically significant (RR, 0.30; P=.13).

Conclusions: This analysis suggests that using metformin in patients treated with AAPs may reduce metabolic risks. Additional randomized controlled trials are needed, but available data support consideration of this intervention in clinical practice.

J Clin Psychiatry

Submitted: April 9, 2009; accepted May 11, 2009.

Online ahead of print: April 6, 2010 (doi:10.4088/JCP.09m05274yel).

Corresponding author: Craig I. Coleman, PharmD, University of Connecticut School of Pharmacy, University of Connecticut/Hartford Hospital Evidence-Based Practice Center, 80 Seymour St, CB309, Hartford, CT 06102-5037 (

J Clin Psychiatry 2010;71(10):1286-1292