Old and new classes of glucose-lowering agents as treatments for non-alcoholic fatty liver disease: A narrative review

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease with a global prevalence of about 55% in people with type 2 diabetes mellitus (T2DM). T2DM, obesity and NAFLD are three closely inter-related pathological conditions. In addition, T2DM is one of the strongest clinical risk factors for the faster progression of NAFLD to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Increasing evidence suggests that newer classes of glucose-lowering drugs, such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter-2 inhibitors, could reduce the rates of NAFLD progression. This narrative review aims to briefly summarize the recent results from randomized controlled trials testing the efficacy and safety of old and new glucoselowering drugs for the treatment of NAFLD or NASH in adults both with and without coexisting T2DM.

The effect of metformin usage on survival outcomes for hepatocellular carcinoma patients with type 2 diabetes mellitus after curative therapy

“…Furthermore, metformin can inhibit energetic metabolism including blood glucose, which may influence the proliferation and migration of HCC cells ( 24 ). Moreover, metformin can control the development of T2DM, thereby repairing the liver injury from DM and HCC ( 25 ). Sun et al.…”

In praise of pioglitazone: An economically efficacious therapy for type 2 diabetes and other manifestations of the metabolic syndrome

“…Non-alcoholic fatty liver disease (NAFLD) has become the world's most common liver disease, with a global prevalence of approximately 55% in patients with type 2 diabetes. 64 NAFLD is characterized by the accumulation of hepatic fat (> 5%) in the absence of alcohol abuse or other chronic liver diseases. The increased frequency of nonalcoholic steatohepatitis (NASH) is closely related to obesity, metabolic syndrome and type 2 diabetes.…”

“…Spence et al, who reported on the efficacy of pioglitazone after a stroke or TIA, suggest that lower doses could ameliorate this risk of bladder cancers. 93 As shown in Figure 2 • Decreased hepatic fat 61 • Decreased hepatic inflammation 61 • No decrease in hepatic fibrosis 61 • Possible effect on hepatic fibrosis when utilized with weight loss/ metformin/exenatide 62 • Probable decreases in cirrhosis and liver cancer 64 Polycystic ovary disease • Decreased insulin resistance 66 • Lower insulin levels 66 • Decreased manifestations of hyperandrogenaemia (acne, hirsutism, amenorrhoea, infertility) 70 • Return of ovulation and restoration of fertility 71 inhibitors when both were compared with sulphonylureas. 93 Like other TZDs, pioglitazone worsens osteoporosis and increases the risk of fracture, possibly through the conversion of osteoblasts to adipocytes.…”

Portal hypertension in nonalcoholic fatty liver disease: Challenges and perspectives

“…However, these pharmacotherapies have not been yet tested for management of PH in the early stages of NAFLD. Most drug candidates for PHT management in the early stages of NAFLD have only been tested in animal models 76 . However, there are some promising drugs for PHT in NAFLD as outlined below.…”

“…Most drug candidates for PHT management in the early stages of NAFLD have only been tested in animal models. 76 However, there are some promising drugs for PHT in NAFLD as outlined below.…”