Abstract
A fourth of the adult population is now suffering from nonalcoholic fatty liver disease (NAFLD) worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to liver-related mortality. NAFLD/NASH is closely associated with type 2 diabetes. Although pioglitazone is now recommended as the 1st line therapy for NASH with type 2 diabetes, pioglitazone has several safety concerns such as body weight gain, heart failure, fluid retention, and bone fracture in women. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have a variety of functions such as glycemic control, bodyweight reduction, and decreased body pressure. Accumulating evidence has shown that this agent has also cardioprotective and renoprotective effects in patients with or without type 2 diabetes. Recent studies that SGLT2 inhibitor can also reduce in transaminase activities or hepatic fat content in NAFLD. NAFLD patients with type 2 diabetes can be indicated for SGLT2 inhibitor, because they are obese, have insulin resistance, and at high risk of cardiovascular events. The phase 3 study of dapagliflozin for NAFLD (DEAN study) is now ongoing. It remains unknown whether this agent can ameliorate hepatic fibrosis in NASH, leading to improved over-all or liver-related survival. Since the leading cause of NAFLD mortality is cardiovascular events, SGLT2 inhibitors will become the 1st line treatment for NAFLD/NASH.
Highlights
Nonalcoholic fatty liver disease (NAFLD) includes10-20% of nonalcoholic steatohepatitis (NASH), which has a high risk of dying from the liver-related disease
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to have multifaceted effects such as weight loss, visceral fat reduction, and blood pressure reduction in addition to blood glucose lowering effects, and large-scale clinical trials have demonstrated the protective effects on organs such as heart and kidney (EMPA-REG outcome, CVD-REAL study, CANVAS program, CREDENCE trial [1], DECLARE trial, DAPA-HF study [2])
Diabetes and Liver Disease According to the cause of death survey of diabetic patients nationwide (2001-1010, n = 45,708), 9.3% died from liver disease (6.0% liver cancer, 3.3% cirrhosis), ranking third after heart disease and pneumonia Met
Summary
10-20% of nonalcoholic steatohepatitis (NASH), which has a high risk of dying from the liver-related disease. According to the phase 3 clinical trial of luseogliflozin, the group treated with luseogliflozin (n = 79) had significantly improved AST, ALT, and GGT compared to placebo [9] These results suggested that the hepatoprotective effect of SGLT2 inhibitors in type 2 diabetes patients. According to a report from Dokkyo University, liver fat measured by FibroScan (CAP) decreased significantly from 314 ± 61 to 290 ± 73 dB/m [15] These results suggested that SGLT2 inhibitors reduce hepatic fat content. The effects of new diabetes drugs, such as DPP4 inhibitor, GLP-1 receptor agonist, an SGLT2 inhibitor, on hepatocarcinogenesis are not clear, but according to a report by Dr Kawaguchi from Kurume University, Fig- 3: Protocol of a phase 2 study of licogliflozin (SGLT1/2 dual inhibitor) for NASH. 76.5% of patients in the higher dose group experienced diarrhea vs ~40% for placebo and low dose group
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
