Effects of metformin on liver fat content in schizophrenia patients with olanzapine-induced weight gain

Abstract

Objective To evaluate the efficacy of metformin on liver fat content in 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/d) (metformin group), the other with olanzapine plus placebo(placebo group) for 16 weeks. All patients continued to maintain the original olanzapine dosage. Liver fat content was measured by MRI at baseline and at the end of 16 weeks, respectively. At the same time, glucose and lipid metabolism (including fasting blood glucose, hemoglobin A1c, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein-cholesterol), homeostasis model assessment of insulin resistance index were measured respectively, analysing the correlation between the change value of LFC and other indicators. Results (1) Over the 16-week study period, LFC value in metformin group decreased compared with baseline ((16.55 ± 7.51)% vs. (19.47 ± 8.99)%,t=2.909, P<0.05).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%CI=-6.08 to -0.93,P=0.009). (2) Compared to baseline, in the metformin group, triglyceride and HOMA-IR reduced significantly, while high density lipoprotein cholesterol increased significantly at weeks 16 (t=2.242, 2.116, 3.226, all P<0.05). (3) There was positive correlation between LFC changes and TG, HOMA-IR changes significantly (r =0.505,0.578, both P<0.05). Conclusion Metformin can significantly attenuate liver fat content in schizophrenia patients with olanzapine-induced weight gain. It may be related to the improvement of the part of the glucolipid metabolic indices. Key words: Metformin; Schizophrenia; Metabolic syndrome; Insulin resistance; Olanzapine; Liver fat content