Novel antidiabetic medications for non‐alcoholic fatty liver disease with type 2 diabetes mellitus

Abstract

Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin, weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to lack of clinical evidence. The effects of pioglitazone on NASH histology with T2DM have been extensively proved, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. In recent years, novel antidiabetic medications have been approved for T2DM, such as glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium/glucose cotransporter 2 inhibitors. A key clinical question for hepatologists is what kinds of antidiabetic medications are the most appropriate for the treatment of NAFLD accompanied by T2DM, to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increased risk of cardiovascular events. This review focuses on novel antidiabetic agents and future perspectives on the treatment of NAFLD/NASH with T2DM.

A novel dual PPAR-γ agonist/sEH inhibitor treats diabetic complications in a rat model of type 2 diabetes

“…Indeed, there are roles for hyperglycaemia and hyperlipidaemia in NAFLD pathogenesis and consequent liver dysfunction and fibrosis [53]. In addition, hyperglycaemia is suggested to contribute to the pathophysiology of liver fibrosis in the metabolic syndrome and type 2 diabetes [62, 63]. Overall, we demonstrated that apart from its ability to treat diabetic nephropathy, RB394 can treat fatty liver and steatohepatitis in type 2 diabetes.…”

Pulsed Electromagnetic Fields Alleviates Hepatic Oxidative Stress and Lipids Accumulation in db/db mice

“…Type 2 diabetes mellitus (T2DM) is the most common form of diabetes with metabolic disturbance. Recently literatures identified that almost 70% of T2DM patients present with non-alcoholic fatty liver disease (NAFLD) and the pathophysiology of NAFLD is still under illumination 1, 2 . A closely connection between NAFLD and T2DM has increasingly been identified.…”

Phase 3 drug pipelines in the treatment of non‐alcoholic steatohepatitis

“…Though antidiabetic or antihyperlipidemic agents on the market are expected to also be useful for NASH, there have been insufficient evidences of their efficacy for the treatment of NASH. 5,6 It is estimated that the drug market for NASH will reach $US45 billion 2027 in the USA, Japan, and EU 5 (England, France, Germany, Italy, and Spain). This review provides an overview of NASH agents currently in phase 3 trials under development (Table 1).…”