Adjunctive Metformin for Antipsychotic-Induced Dyslipidemia: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Abstract

Background: Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials (RCTs) to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. Methods: The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5*3 version software. The primary outcome was the change of serum lipid level. Results: Twelve studies with 1,215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol [SMD: -0*37 (95%CI:-0*69, -0*05), P=0*02; I2=78%], total cholesterol [SMD: -0*47 (95%CI:-0*66, -0*29), P<0*00001; I2=49%], triglyceride [SMD: -0*33 (95%CI:-0*45, -0*20), P<0*00001; I2=0%], and high density lipoprotein cholesterol [SMD: 0*29 (95%CI:0*02, 0*57), P=0*03; I2=69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P=0*002 to 0*01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P=0*07 to 0*33). The rates of discontinuation due to any reason [RR: 0*97 (95%CI: 0*66, 1*43), P=0*89; I2=0%] was similar between the two groups. Conclusions: Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia. Funding Statement: The study was supported by the National Key and Development Plan Precision Medical Research 2016 Project (2016YFC0906302) and Science and Technology Program of Guangzhou (201807010064). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Review registration: CRD42019125861.