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Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): -10.0 IU/L, 95%CI -12.2 to -7.79 IU/L; I² = 10.5%) and gamma-glutamyltransferase levels (WMD: -14.49 IU/L, 95%CI -19.35 to -9.63 IU/L, I² = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: -2.05%, 95%CI -2.61 to -1.48%; I² = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD.

SUBMITTER: Mantovani A

PROVIDER: S-EPMC7823667 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.

Mantovani Alessandro A Petracca Graziana G Csermely Alessandro A Beatrice Giorgia G Targher Giovanni G

Metabolites 20201230 1

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum ...[more]

PMID: 33396949

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Project description:BackgroundThe clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the effect of SGLT2 inhibitors on cardiovascular outcomes and safety events, giving particular attention to the benefits in subgroups of patients with different diseases.MethodRandomized controlled trials (RCTs) reporting cardiovascular outcomes following the administration of SGLT2 inhibitors and placebo were included in this study. Cardiovascular outcomes included all-cause death, major adverse cardiovascular events (MACEs), cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF). We also focused on the cardiovascular benefits of SGLT2 inhibitor application in subgroups of patients with different diseases, including type 2 diabetes (T2D), heart failure (HF), high risk of atherosclerotic cardiovascular disease (ACD), diagnosed ACD, and chronic kidney disease (CKD). Safety events associated with SGLT2 inhibitors, including acute kidney injury (AKI), diabetic ketoacidosis (DKA), hypoglycemia, urinary tract infection, thromboembolic event, bone fracture, volume depletion, and amputation, were also reported.ResultsThis meta-analysis included 15 RCTs with 78,212 participants. SGLT2 inhibitors reduced the risk of all-cause death (RR 0.89; 95% CI: 0.85-0.94; I2 = 32%; p < 0.01), CV death (RR 0.87; 95% CI: 0.82-0.93; I2 = 11%; p < 0.01), MACEs (RR 0.89; 95% CI: 0.84-0.94; I2 = 46%; p < 0.01), HHF (RR 0.70; 95% CI: 0.66-0.74; I2 = 0%; p < 0.01), and AKI (RR 0.81; 95% CI: 0.73-0.90; I2 = 0%; p < 0.01) but increased the risk of DKA (RR 2.56; 95% CI: 1.72-3.80; I2 = 0%; p < 0.01). However, no apparent benefit in MI and stroke was observed between the SGLT2 inhibitor and control groups. SGLT2 inhibitors reduced the risk of all-cause death, MACEs, CV death, and HHF in diabetic patients; reduced the risk of all-cause death, MACEs, CV death, MI, and HHF in primary prevention; reduced the risk of all-cause death, CV death, and HHF in patients with ACD and HF; and reduced the risk of MACEs, CV death, and HHF in patients with CKD.ConclusionSGLT2 inhibitors have a positive effect in reducing the risk of all-cause death, CV death, MACE, HHF, and AKI and increasing the risk of DKA. The application of SGLT2 inhibitors in the primary prevention of ACD also has certain clinical benefits in reducing MI.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306490].

Dataset Information

Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.

Publications

Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.

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