Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis

Preliminary evidence suggests that inhibition of dipeptidyl peptidase (DPP)-IV preserves pancreatic beta cell function in patients with type 2 diabetes (T2D). However, its effects on liver histology in nonalcoholic steatohepatitis (NASH), hepatic complication of diabetes, have not yet been adequately explored. The present open-label, single-arm observational pilot study investigated the effects of one year of treatment with a dipeptidyl peptidase-IV inhibitor, sitagliptin, on liver histology, body mass index (BMI), and laboratory parameters in NASH patients with T2D. Paired liver biopsies from 15 diabetic patients with NASH (7 males, 8 females; mean age: 49.7 +/- 8.1 years (range: 36-62)) before and after one year of therapy with sitagliptin 100 mg once daily were studied. Clinical and laboratory parameters were recorded. Treatment with sitagliptin resulted in a significant decrease in ballooning (P = 0.014) and NASH scores (P = 0.04), while the reduction in the steatosis score was of borderline statistical significance (P = 0.054). These effects were accompanied by a significant reduction in body mass index, AST, and ALT levels. Our study suggests that sitagliptin ameliorates liver enzymes and hepatocyte ballooning in NASH patients with T2D and may have therapeutic implications.