scholarly journals Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 2 (S1) ◽  
pp. 17-25
Author(s):  
Sumida Y ◽  
Yoneda M ◽  
Tokushige K ◽  
Kawanaka M ◽  
Fujii H ◽  
...  

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.

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.


JGH Open ◽  
2021 ◽  
Author(s):  
Mohammad Shafi Kuchay ◽  
Narendra Singh Choudhary ◽  
Sunil Kumar Mishra ◽  
Tarannum Bano ◽  
Sakshi Gagneja ◽  
...  

Diabetes Care ◽  
2021 ◽  
pp. dc210131
Author(s):  
Chi-Ho Lee ◽  
Wai-Kay Seto ◽  
David Tak-Wai Lui ◽  
Carol Ho-Yi Fong ◽  
Helen Yilin Wan ◽  
...  

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.


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