Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor

Abstract

We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 (SGLT2) inhibitor. Five SGLT2 inhibitor (luseogliflozin, dapagliflozin, tofogliflozin, empagliflozin and canagliflozin) preparations and five DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, anagliptin and linagliptin) preparations were used. The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI, hemoglobin A1c (HbA1c) also decreased, but not to a significant extent. However, decreases of the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γ-GTP) and uric acid were observed in this group. On the other hand, in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor, significant decrease of the HbA1c was observed, indicating the favorable effect of the concomitant therapy. The body weight and BMI decreased. As for the serum lipid profile, elevation of the serum HDL-cholesterol (HDL-C) was observed. Furthermore, AST, ALT, γ-GTP and uric acid decreased in the combined treatment group. Then, the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed. The results showed that concomitant administration of sitagliptin, a DPP-4 inhibitor, with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile.

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…Previous studies have examined the effects of various SGLT2 inhibitors on patients with T2DM and NAFLD [ 18 , 43 , 49 – 52 ]. They showed improvement in at least one liver enzyme level [ 31 , 43 , 49 , 50 , 52 ] and in hepatic fat content [ 43 , 49 , 52 ]. An absolute reduction in liver fat content has been reported in patients with NAFLD treated with empagliflozin in the E-LIFT Trial.…”

Comparative effect of dipeptidyl-peptidase 4 inhibitors on laboratory parameters in patients with diabetes mellitus

“…However, the mean changes in AST and ALT concentrations showed no significant difference among the five groups of DPP-4 inhibitor users. Kusunoki et al previously reported that serum AST, ALT, and γ-GT concentrations were significantly decreased in patients with 6-month administration of combination therapy with a DPP-4 inhibitor and a sodium glucose co-transporter 2 (SGLT2) inhibitor [21]. Aoki et al previously reported that serum ALT and γ-GT concentrations were significantly decreased in patients with 16-week administration of combination therapy with alogliptin and pioglitazone compared with those with monotherapy [22].…”

Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review

“…Four of these reported randomized, controlled, double-blind studies of liraglutide with a placebo (n = 3) or active (n = 1) comparator, and only one of these, the "Liraglutide Safety and Efficacy in Patients with Non-alcoholic Steatohepatitis (LEAN)" study, assessed histological endpoints using biopsy. Of note, of studies investigating liraglutide, only Insufficient data: 3 of 6 studies suggest modest benefit (7,36,38) and the other 3 suggest no benefit over comparator (30,37,59) Topiramate…”

“…They were developed for the treatment of type 2 diabetes mellitus (T2D), but recent literature suggests pleiotropic effects including potential cardiovascular benefit and modest weight loss (79,80). Six studies have examined the effects of various SGLT2 inhibitors on patients with T2D and NAFLD (7,30,(36)(37)(38)59), but none to date have included histologic endpoints by biopsy. Five of the studies suggest improvement in at least one liver enzyme (7,30,(36)(37)(38)59), two showed improvement of hepatic fat content measured by liver-to-spleen ratio (30,59), and one, the "Effect of Empagliflozin on Liver Fat in Patients with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease (E-LIFT)" trial, showed improvement of hepatic fat content measured by MRI-PDFF (36).…”