Open AccessImpact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase‐4 in patients with type 2 diabetes and non‐alcoholic fatty liver disease
Author(s) -
Aso Yoshimasa,
Kato Kanako,
Sakurai Shintaro,
Kishi Haruka,
Shimizu Masanori,
Jojima Teruo,
Iijima Toshie,
Maejima Yuko,
Shimomura Kenju,
Usui Isao
Publication year - 2019
Publication title -
international journal of clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 98
eISSN - 1742-1241
pISSN - 1368-5031
DOI - 10.1111/ijcp.13335
Subject(s) - dapagliflozin , medicine , endocrinology , type 2 diabetes , fatty liver , steatosis , insulin resistance , dipeptidyl peptidase 4 , adipose tissue , diabetes mellitus , insulin , disease
Aims Soluble dipeptidyl peptidase‐4 (sDPP‐4) is secreted by hepatocytes and induces adipose tissue inflammation and insulin resistance. Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors can improve hepatic steatosis by inhibiting hepatic de novo lipogenesis. We investigated the effects of dapagliflozin (an SGLT2 inhibitor) on serum levels of sDPP‐4 in patients with type 2 diabetes and non‐alcoholic fatty liver disease (NAFLD). Methods Fifty‐seven patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin group (5 mg/d for 24 weeks) (n = 33) or the control group (n = 24). Serum levels of sDPP‐4 were measured with a commercial ELISA kit. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by dual bioelectrical impedance analysis. Results In a total of 57 patients, baseline serum sDPP‐4 was positively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ‐glutamyl transferase (GGT) and HOMA‐IR Both VAT and SAT areas decreased significantly in the dapagliflozin group alone. Liver enzymes were decreased at 24 weeks in the dapagliflozin group, but were unchanged in the control group. Although both groups showed significant reduction of serum sDPP‐4 after 24 weeks of treatment, the magnitude of decrease was significantly larger in the dapagliflozin group. Changes in liver enzymes during treatment with dapagliflozin were positively correlated with the change in serum sDPP‐4, but not with changes in VAT volume or HbA1c. Conclusions Improvement of liver dysfunction after treatment with dapagliflozin was associated with a decrease in serum sDPP‐4, suggesting that reduction of serum sDPP‐4 by SGLT2 inhibitors may be a therapeutic strategy for NAFLD/NASH in patients with type 2 diabetes that is independent of glucose lowering or weight loss.