Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis

center dot Olanzapine in an atypical antipsychotic agent which is associated with significant weight gain. center dot Metformin, an anti-hyperglycaemic agent, has been used to treat or prevent weight gain associated with olanzapine. center dot Meta-analyses on studies that have examined the use of metformin for treatment of antipsychotic-induced weight gain report significant heterogeneity. WHAT THIS STUDY ADDS center dot Systematic review and meta-analysis showed that metformin is useful for the short-term treatment of olanzapine-induced weight gain. Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n = 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P = 0.00002, I2 = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m-2 lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.