Meta-analysis Of The Effect Of SGLT2 Inhibitors On Hepatic Fibrosis In Patients With T2DM Complicated With NAFLD

Background: Non-alcoholic fatty liver disease(NAFLD)is a chronic and unstable metabolic complication caused by diabetes,which is characterized by hepatic steatosis,inflammation and fibrosis.Sodium and glucose cotransporter2(SGLT2)inhibitors have been shown to be beneficial in some clinical trials in patients with glycosuria complicated with NAFLD.Because these studies are still in the initial stage,few and single studies have been conducted.At present,the effects of SGLT2 inhibitors on type 2 diabetes mellitus(T2DM)complicated with NAFLD,especially its effect on liver fibrosis,have not been recognized.Objective: To analyze the effects of SGLT2 inhibitors on the indexes of liver fibrosis in patients with T2 DM complicated with NAFLD,and to observe the effects of liver enzymes and liver fat.The main outcome was the changes of liver fibrosis index,liver enzyme and liver fat.The secondary outcome was changes in risk factors for NAFLD,including body weight,lipid distribution,visceral fat,glycosylated hemoglobin,and insulin resistance index.Methods: The Pubmed,Embase and Cochrane databases were searched systematically,and the starting and ending time of literature retrieval was from the establishment of the database to October 2020.Random effects model combines data with weighted mean difference(MD)and 95% confidence interval(CI).Meta analysis was performed with Rev Man 5.3statistical software.Results: This study included 9 RCT studies with a total of 461 patients.Meta analysis showed that SGLT2 inhibitor could significantly reduce the level of hepatic fibrosis index(FIB-4:MD-0.25,95%CI-0.39,-0.11,P =0.0007;serum type Ⅳ collagen 7s: MD-0.32,95%CI-0.59,-0.04,P =0.02;ferritin:MD-26.7,95%CI-50.64,2.76,P = 0.03).SGLT2 inhibitors could significantly reduce the level of liver enzymes(ALT:MD-3.49,95%CI-5.1,1.58,P < 0.0001;AST:MD-3.64,95%CI-5.10,-2.18,P < 0.00001;GGT:MD-7.13,95%CI-12.95,-1.32,P = 0.02).SGLT2 inhibitor could significantly reduce the level of liver fat(L/S:MD 0.16,95% CI0.10,0.22,P < 0.00001;MRI-PDFF:MD-1.97,95%CI-3.49,-0.45,P = 0.01;CAP:MD-0.29,95%CI-26.95,-13.64,P <0.00001;NAFLD score: MD-0.55,95%CI1.04,-0.05,P = 0.03;FLI:MD-11.21,95%CI-16.53,-5.89,P < 0.0001).In addition,aloe extract analysis showed that SGLT2 inhibitors significantly improved metabolic indexes including body weight,VFA,Hb A1 c,HOMA-IR,LDL,HDL and TG.Conclusion: SGLT2 inhibitors can improve liver fibrosis,liver enzymes,liver fat and metabolic indexes in patients with T2 DM complicated with NAFLD,which has guiding significance for the application of SGLT2 inhibitors in the treatment of NAFLD.