Efficacy and safety of sodium-glucose co-transporter 2 inhibitors in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease: A meta-analysis

Objective To systematically review the efficacy and safety of sodium-glucose co-transporter 2( SGLT2) inhibitors in the treatment of type 2 diabetes mellitus( T2 DM) with nonalcoholic fatty liver disease( NAFLD). Methods Foreign databases( PubMed,Cochrane Library,and Embase) and Chinese databases( CNKI,VIP,and Wanfang Data) were searched for articles published up to March2020. Keywords were used to screen out eligible studies,related scales were used to evaluate the quality of articles,and RevMan 5. 3 and Stata 15. 0 were used to perform the meta-analysis. Results A total of 9 cohort studies and 5 randomized controlled trials( RCTs) were included,with 605 patients in total. The meta-analysis of main observation indices showed that SGLT2 inhibitors significantly inhibited alanine aminotransferase( ALT)( mean difference [MD]=-24. 22,95% confidence interval [CI]:-29. 54 to-18. 89,P < 0. 001) and hemoglobin A1 c( Hb A1 c)( MD =-0. 53,95% CI:-0. 74 to-0. 32,P < 0. 001) in cohort studies,as well as ALT( MD =-12. 51,95% CI:-15. 61 to-9. 41,P < 0. 001) and HbA1 c( MD =-0. 54,95% CI:-0. 80 to-0. 27,P < 0. 001) in RCTs. The analysis of secondary observation indices showed that SGLT2 inhibitors significantly improved body mass index( P < 0. 001),fat mass( P < 0. 001),hepatic fat fraction( P < 0. 001),gamma-glutamyl transpeptidase( P < 0. 001),fasting blood glucose( P < 0. 001),serum ferritin( P <0. 001),and serum type Ⅳ collagen 7 S( P = 0. 02). There was a significant difference in the result of the meta-analysis of aspartate aminotransferase between RCTs( P = 0. 16) and cohort studies( P < 0. 001). After the administration of SGLT2 inhibitors,there were significant increases in the incidence rates of decreased body fluid volume( risk ratio [RR]= 7. 67,95% CI: 1. 45-40. 42,P = 0. 02),urinary tract infection( RR = 4. 27,95% CI: 1. 11-16. 43,P = 0. 03),and reproductive system infection( RR = 3. 76,95% CI: 1. 21-11. 69,P =0. 02). Conclusion Current evidence suggests that SGLT2 inhibitors can reduce body mass,blood glucose,liver enzymes,and liver fat content in patients with T2 DM and NAFLD and improve liver fibrosis to a certain degree,but they can increase the risk of fluid loss and reproductive system infection in patients. More studies are needed for further verification.