Metformin Attenuates Liver Fat Content: Finding from Schizophrenia Patients with Olanzapine-induced Weight Gain

Abstract

Objective: This study was performed to evaluate the efficacy of metformin on liver fat content (LFC) in first episode schizophrenia patients with olanzapine-induced weight gain, and the relationship between the change of LFC and the other metabolic indices.

Methods: In a double-blind study, the clinically stable inpatients with first-episode schizophrenia under olanzapine monotherapy who gained more than 7% of their baseline weight were randomly assigned to two groups; one with olanzapine plus metformin (1,000 mg/day) (metformin group) and the other with olanzapine plus placebo (placebo group) for 16 weeks. All patients continued to maintain the original olanzapine dosage. LFC was measured by magnetic resonance imaging at baseline and at the end of 16 weeks, respectively. At the same time, glucose and lipid metabolism, homeostasis model assessment of insulin resistance index (HOMA-IR) were measured respectively, analyzing the correlation between the change value of LFC and other indicators.

Results: Over the 16-week study period, LFC value in metformin group decreased compared with baseline. LFC change across the 16-week treatment period was -2.91% for the metformin group and 0.59% for the placebo group, with a between-group difference of -3.5% (95% confidence interval, -6.08 to -0.93; p = 0.009). Compared to baseline, in the metformin group, triglyceride and HOMA-IR reduced significantly, while high density lipoprotein cholesterol increased significantly at weeks 16. There was positive correlation between LFC changes and triglycerides, HOMA-IR changes significantly.

Conclusion: Metformin can significantly attenuate LFC in schizophrenia patients with olanzapine-induced weight gain. It may be related to the improvement of the part of the glucolipid metabolic indices.

Keywords: Insulin resistance; Liver fat.; Metabolic syndrome; Metformin; Olanzapine; Schizophrenia.

Fig. 1

Effects of 16 weeks of treatment with metformin or placebo on liver fat content (LFC). Each point represents mean ± standard deviation based on mixed model repeated measures analysis. Time (week) effect: F = 3.956, degree of freedom (df) = 1, p = 0.056 (non-significant); drug × time effect from mixed model analysis of variance: F = 8.437, df = 1, p < 0.01.