Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Hepatic Fibrosis in Patients With Type 2 Diabetes: A Chart-Based Analysis

Abstract

Background:The presence of nonalcoholic fatty liver diseases (NAFLDs) and type 2 diabetes was associated with elevated risks of cardiovascular events as well as the progression of NAFLD to fibrosis/cirrhosis and hepatocellular carcinoma. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a widely used antidiabetic drug, which promotes urinary excretion of glucose. Recent animal and human studies demonstrated the beneficial effects of SGLT2is on lipid accumulation and fibrosis in the liver. The purpose of the current study was to elucidate the effects of SGLT2is on hepatic fibrosis in the realworld setting. Methods:We selected patients with type 2 diabetes who had been prescribed SGLT2is continuously for 12 months between April 1, 2014 and March 31, 2018 by a chart-based analysis. We compared the data before the SGLT2is treatment with the data at 6 and 12 months after the SGLT2is treatment started. Fibrosis in the liver was evaluated by fibrosis-4 (FIB4) index. Results:We enrolled 315 patients in this study. The body weight, body mass index (BMI), serum levels of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transferase were significantly decreased at 6 months and maintained at 12 months, whereas there was no significant change in FIB4 index. We divided the studied patients into three groups according to the baseline FIB4 index. Only in the group of high value of the baseline FIB4 index, FIB4 index was significantly decreased at 12 months. The correlations between the change of FIB4 index during 12-month SGLT2i treatment was correlated inversely with the baseline FIB4 index. Conclusion:Present study demonstrated that SGLT2i could ameliorate fibrosis in the liver in high-risk patients for hepatic fibrosis.

Effects of a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Pemafibrate, on Metabolic Parameters: A Retrospective Longitudinal Study

“…Because we previously reported that SGLT2i improves atherogenic dyslipidemia, liver function and serum UA in addition to glucose-lowering [ 17 , 18 , 19 , 20 ], we analyzed changes in metabolic parameters after the start of pemafibrate by dividing patients into patients who received SGLT2i and patients who did not receive SGLT2i ( Table 3 ).…”

“…Interestingly, a significant decrease in AST was observed only in patients who received SGLT2i. Since SGLT2i improve liver function [ 17 , 18 , 19 , 20 ], synergism and/or the possible interaction between pemafibrate and SGLT2i may be associated with a decrease in AST, which still needs further studies. Accumulated data suggest that NAFLD is induced by abnormal hepatic lipid metabolism such as an increase of intra-hepatic fat content [ 46 ].…”

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…While some studies did not find a significant change from baseline in liver fibrosis [ 43 , 69 , 70 ], others reported SGLT2 inhibitors effectively decrease the FIB-4 index. [ 18 , 71 ]. In another study, the APRI index decreased significantly with pioglitazone [ 72 ].…”

Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

“…Using the FIB-4 index, a validated marker of liver fibrosis, several studies found no significant effects compared with baseline or use of other glucose-lowering agents [ 20 , 32 – 34 ]. Nevertheless, two studies demonstrated a significant reduction in FIB-4 index with SGLT2 inhibitor [ 35 , 36 ]. In our study there were no significant changes in non-invasive parameters according to the NAFLD fibrosis score, FIB-4 index, and APRI.…”