Efficacy of alogliptin in preventing non-alcoholic fatty liver disease progression in patients with type 2 diabetes

Abstract

Abstract. Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective antifibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes. The study was a single arm, multi-centre, non-randomised study of NAFLD patients with type 2 diabetes. NAFLD was diagnosed according to ultrasonographic findings. All the patients received 25 mg/day of alogliptin for 12 months. The efficacy of alogliptin in preventing NAFLD progression was assessed using overall NAFIC scores [non-alcoholic steatohepatitis (NASH), ferritin, insulin and type IV collagen 7S] and individual component scores according to baseline haemoglobin A1c (HbA1c) levels. Of the 39 patients enrolled in the study, 16 patients (40.3%) had NAFIC scores >2 points, indicating the presence of NASH. NAFIC scores markedly decreased following 12 months of alogliptin administration, but remained >2 points in 10 patients, indicating that NASH may have persisted in these patients. The relative risks for persistent NASH were 4.92 (95% confidence interval, 0.61-40.0) in the highest HbA1c tertile group compared with those in the lowest group. However, no statistically significant linear trend was observed across all HbA1c categories (P=0.145). DPP4-I may have efficacy against NAFLD progression in patients with type 2 diabetes with relatively lower HbA1c levels. DPP4-I may represent a potential new therapeutic strategy for the prevention of disease progression in NAFLD patients with type 2 diabetes.

Dipeptidyl peptidase 4 inhibitors attenuates the decline of skeletal muscle mass in patients with type 2 diabetes

“…Expression of DPP4 increases in the liver of patients with non‐alcoholic fatty liver disease, and inhibition of DPP4 reduces a hepatic fat accumulation in mouse models of fatty liver disease . In addition, some clinical studies showed beneficial effects of incretin mimetics on the hepatic steatosis and serum transaminase activity . However, to our knowledge, no data are available regarding the impact of DPP4 inhibitors on human liver histology including steatosis in randomized controlled trials.…”

The effect of antidiabetic medications on non-alcoholic fatty liver disease (NAFLD)

“…There are even fewer studies supporting the effect of other types of DPP-4 in NAFLD: in a double-blind RCT involving 44 patients with well-controlled T2DM vildagliptin was proven to reduce liver trygliceride content assessed by MRI along with achieving a significant improvement in serum transaminase and fasting plasma glucose after a 6-month course; [93] for alogliptin evidence of any effects in NAFLD is poor [94].…”

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

“…In contrast, two studies from Japan denied the effect of 1 year of treatment with sitagliptin (50 mg/day) on serum transaminase in NAFLD patients. Recently, alogliptin, another DDP‐4 inhibitor, was shown to decrease the NAFIC score (NASH, ferritin, insulin, and type 4 collagen 7S), which JSG‐NAFLD has developed to differentiate NASH from NAFLD without liver biopsies (Table ) . The results of two RCTs from the USA regarding the effect of DPP‐4 inhibitors on T2DM patients with NAFLD are conflicting …”