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

Masataka Kusunoki; Yukie Natsume; Tetsuro Miyata; Kazuhiko Tsutsumi; Yoshiharu Oshida

doi:10.1055/a-0585-0145

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2018; 68(12): 704-709
DOI: 10.1055/a-0585-0145

Original Article

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

Autoren

Masataka Kusunoki

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan
Yukie Natsume

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan
Tetsuro Miyata

²Vascular Center, Sanno Medical Center, Tokyo, Japan
Kazuhiko Tsutsumi

³Okinaka Memorial Institute for Medical Research, Tokyo, Japan
Yoshiharu Oshida

¹Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

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.

Key words

monotherapy - concomitant therapy - HbA1c - HDL cholesterol

Volltext

Referenzen

References
1 Wright EM. Glucose transport families SLC5 and SLC50. Mol Aspects Med 2013; 34: 183-196
2 Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794
3 DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012; 14: 5-14
4 Seino Y, Sasaki T, Fukatsu A. et al. Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, phase 3 study. Curr Med Res Opin 2014; 30: 1245-1255
5 Zinman B, Wanner C, Lachin JM. et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-2128
6 Kim YG, Hahn S, Oh TJ. et al. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: A systematic review and meta-analysis. Diabetologia 2013; 56: 696-708
7 Esposito K, Cozzolino D, Bellastella G. et al. Dipeptidyl peptidase-4 inhibitors and HbA1c target of<7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes Metab 2011; 13: 594-603
8 Shah Z, Kampfrath T, Deiuliis JA. et al. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation 2011; 124: 2338-2349
9 Monami M, Lamanna C, Desideri CM. et al. DPP-4 inhibitors and lipids: Systematic review and meta-analysis. Adv Ther 2012; 29: 14-25
10 Kusunoki M, Sato D, Natsume Y. et al. Luseogliflozin, a sodium glucose co-transportet 2 inhibitor, alleviates hepatic impairment in Japanese patients with type 2 diabetes mellitus. Drug Res 2016; 66: 603-606
11 Merovci A, Solis-Herrera C, Daniele G. et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014; 124: 509-514
12 Rosenstock J, Hansen L, Zee P. et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: A randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 2015; 38: 376-383
13 Scheen AJ. DPP4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects. Expert Opin Drug Metab Toxicol 2016; 12: 1407-1417
14 Chiho Y, Samukawa Y, Sakai S. et al. SGLT-2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos 2014; 35: 391-404