Objective: Serum levels of soluble DPP-4/CD26 are elevated in patients with type 2 diabetes and nonalcoholic fatty disease (NAFLD). Hepatocyte-secreted sDPP-4 induce directly adipose inflammation and insulin resistance in the liver. SGLT2 inhibitors reduce hepatic steatosis by inhibiting hepatic de novo lipogenesis. We investigated effects of dapagliflozin, an SGLT2 inhibitor, on liver dysfunction, hepatic steatosis, and serum levels of sDPP-4 in patients with type 2 diabetes and NAFLD.
Methods: Fifty-seven patients with type 2 diabetes and NAFLD were randomized into a dapagliflozin (5 mg/day) treatment group (n=33) or an active placebo group (n=24) for 24 weeks. Visceral adipose tissue (VAT) volumes were measured using a dual bioelectrical impedance analysis. Hepatic steatosis was evaluated by controlled attenuated parameter (CAP) using a transient elastography.
Results: At baseline, serum sDPP-4 showed positive correlations with AST, ALT, GGT, and HOMA-IR in a total of 57 patients. VAT significantly decreased in the dapagliflozin group, but not in the placebo group. AST, ALT, and GGT showed a significant decrease at 24 weeks in the dapagliflozin group, while they were unchanged in the control group. CAP also significantly decreased in the dapagliflozin group. Although both groups showed a significant reduction in serum sDPP-4 at 24 weeks after treatment, the magnitude of sDPP-4 reduction was greater in the dapagliflozin group. Changes in liver enzymes after dapagliflozin treatment correlated positively with those in serum sDPP-4 levels, but not those in VAT or HbA1c.
Conclusions: An improvement of liver dysfunction was associated with a decrease in serum sDPP-4, but not that in VAT or HbA1c, after treatment with dapagliflozin in these patients, suggesting that reducing serum sDPP-4 by SGLT2 inhibitors may be a therapeutic strategy for treatment of NAFLD/NASH in people with type 2 diabetes.
K. Kato: None. Y. Aso: Research Support; Self; Ono Pharmaceutical Co., Ltd. T. Jojima: None. T. Iijima: None. I. Usui: None.