Meta-analysis Of Metformin For Improving Efficacy And Safety Of Clozapine-related Metabolic Syndrome

Background: Clozapine is currently the most effective drug for the treatment of refractory schizophrenia,and its efficacy is accompanied by metabolic problems.Among them,the metabolic syndrome with the main manifestations of weight gain,abnormal blood glucose,and lipids is increasingly receiving attention.At present,the most widely used oral hypoglycemic agent metformin,some studies suggest that can be used to improve clozapine-induced glucose and lipid metabolism and weight loss,but the results are different,the safety of doubt.Objective: To compare the efficacy and safety of metformin with placebo for the improvement of metabolic syndrome caused by clozapine.Methods: A randomized controlled trial of metformin and placebo in the treatment of metabolic syndrome caused by clozapine was conducted by computer-based retrieval of domestic and foreign databases.The retrieved literature was selected for meta-analysis according to pre-designed inclusion and exclusion criteria.Search Pubmed,Embase,Cochrane Library and Wanfang Database,China Sci-Tech Periodical Database,China Biomedical Literature Service System and China Knowledge Resource Pool.Use the review manager 5.3 statistical software for analysis.Results: A total of 103 articles were retrieved,including 39 in English and64 in Chinese.After analysis and elimination,12 articles were finally included,a total of 894 cases.The effect of metformin on weight loss was statistically significant compared with the control group(RR:-3.03,95%CI: [-3.85,-2.21]P=0.29,n=546).The effect of metformin on weight loss was higher than that of the control group.group.The effect of metformin on body mass index was statistically significant(RR:-1.11,95% CI: [-1.38,-0.85] P=0.07,n=481).The effect of metformin on waist circumference was statistically significant(RR:-2.65,95% CI: [-3.84,-1.45] P=0.14,n=475).The effect of metformin on fasting blood glucose was statistically significant(RR:-0.91,95% CI: [-1.69,-0.13] P=0.02,n=869).The difference in insulin resistance index between the metformin group was statistically significant(RR:-2.95% CI: [-3.08,-0.91]P<0.00001,n=182).There was a statistically significant difference in the effect of metformin on cholesterol(RR:-0.64,95% CI: [-1.25,-0.04] P = 0.04,n =472).The effect of metformin on triglycerides was statistically significant(RR:-0.48,95% CI: [-0.68,-0.28] P<0.00001,n=624).The effect of metformin on LDL and HDL was not statistically significant(RR:-0.39,95%CI: [-0.77,-0.00]P=0.05,n=335)(RR:-0.02,95% CI: [-0.1,0.06] P = 0.58,n = 315).The effect of metformin on blood pressure was not statistically significant(systolic pressure RR:-0.02,95% CI: [–0.60,0.57] P=0.96,n=355)(diastolic RR:-0.26,95% CI: [-0.81,0.29] P=0.36,n= 355).There was no significant difference inthe adverse effects of metformin or placebo in combination with clozapine(RR:1.03,95% CI: [0.78,1.36] P=0.97,n=3642).Conclusion: Metformin is better than control in improvement of BW,BMI,FBG,HOMA-IR,WC,LDL,TC and TG caused by clozapine.There is no significant difference in BP,HDL and adverse reactions.Its tolerability is comparable to placebo.