Teneligliptin: Expectations for its pleiotropic action

Expert Opinion on Pharmacotherapy

Volumn 16, Issue 3, 2015, Pages 417-426

  Morishita, Ryuichi ^a   Nakagami, Hironori ^a  

^a OSAKA UNIVERSITY MEDICAL SCHOOL   (Japan)

Author keywords

Diabetes mellitus; Dipeptidyl peptidase 4 inhibitors; Glucose fluctuations; Glycemic control; Teneligliptin; Vascular function

Indexed keywords

DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCOSE; TENELIGLIPTIN; 3-(4-(4-(3-METHYL-1-PHENYL-1H-PYRAZOL-5-YL)PIPERAZIN-1-YL)PYRROLIDIN-2-YLCARBONYL)THIAZOLIDINE; ANTIDIABETIC AGENT; GLUCOSE BLOOD LEVEL; PYRAZOLE DERIVATIVE; THIAZOLIDINE DERIVATIVE;

DIABETES MELLITUS; DISEASES; DRUG EFFICACY; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; NON INSULIN DEPENDENT DIABETES MELLITUS; PLEIOTROPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; VASCULAR DISEASE; VASCULAR ENDOTHELIUM; CARDIOVASCULAR DISEASES; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS;

BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; PYRAZOLES; THIAZOLIDINES;

EID: 84921515624     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2015.1000301     Document Type: Review

References (39)

1. Del Prato S. In search of normoglycaemia in diabetes: controlling postprandial glucose. Int J Obes Relat Metab Disord 2002;26:S9-S17
2. International Diabetes Federation. Guideline for management of post meal glucose in diabetes. International diabetes federation. 2011. Available from: http://www.idf.org/2011-guideline-management-postmeal-glucose-diabetes •• An international guideline that describes the effects of post-meal glucose fluctuations on oxidative stress and endothelial dysfunction.
3. Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 2010;33(7):1389-94
4. Risso A, Mercuri F, Quagliaro L, et al. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab 2001;281(5):E924-30
5. Piconi L, Quagliaro L, Da Ros R, et al. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly (ADP-ribose) polymerase. J Thromb Haemost 2004;2(8):1453-9
6. Mita T, Otsuka A, Azuma K, et al. Swings in blood glucose levels accelerate atherogenesis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun 2007;358(3):679-85
7. Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008;57(5):1349-54
8. Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006;295(14):1681-7
9. Su G, Mi SH, Tao H, et al. Impact of admission glycemic variability, glucose, and glycosylated hemoglobin on major adverse cardiac events after acute myocardial infarction. Diabetes Care 2013;36(4):1026-32 •• A study in Chinese AMI patients that showed that glycemic variability was a strong predictor for adverse cardiac outcomes.
10. Balakumar P, Dhanaraj SA. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials. Cell Signal 2013;25(9):1799-803
11. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33(2):187-215
12. Aroor AR, Sowers JR, Jia G, et al. Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol 2014;307(4):H477-92
13. van Genugten RE, Möller-Goede DL, van Raalte DH, et al. Extra-pancreatic effects of incretin-based therapies: potential benefit for cardiovascular-risk management in type 2 diabetes. Diabetes Obes Metab 2013;15(7):593-606
14. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369(14):1327-35
15. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369(14):1317-26
16. Goda M, Kadowaki T. Teneligliptin for the treatment of type 2 diabetes. Drugs Today (Barc) 2013;49(10):615-29 •• Monograph overviewing data on the efficacy, safety and pharmacokinetic/pharmacodynamic characteristics of teneligliptin in the treatment of T2DM.
17. Fukuda-Tsuru S, Anabuki J, Abe Y, et al. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol 2012;696(1-3):194-202 • A study that characterized the pharmacological profiles of teneligliptin in vitro and in vivo.
18. Nabeno M, Akahoshi F, Kishida H, et al. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem Biophys Res Commun 2013;434(2):191-6 •• A study of the structural and binding properties of DPP-4 inhibitors, that demonstrated teneligliptin is a potent, selective, and long-lasting inhibitor of DPP-4.
19. Fukuda-Tsuru S, Kakimoto T, Utsumi H, et al. The novel dipeptidyl peptidase-4 inhibitor teneligliptin prevents high-fat diet-induced obesity accompanied with increased energy expenditure in mice. Eur J Pharmacol 2014;723:207-15
20. Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept 1999;85(1):9-24
21. Liu WJ, Xie SH, Liu YN, et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther 2012;340(2):248-55
22. Pharmaceuticals and Medical Devices Agency. Tenelia application document. 2012. Available from: http://www.pmda.go.jp/english/service/pdf/drugs/tenelia-jun2012-e.pdf
23. Yoshida T, Akahoshi F, Sakashita H, et al. Discovery and preclinical profile of teneligliptin(3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl) piperazin-1-yl]pyrrolidin-2-ylcarbonyl] thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg Med Chem 2012;20(19):5705-19
24. Nakamaru Y, Hayashi Y, Ikegawa R, et al. Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin in humans. Xenobiotica 2014;44(3):242-53 •0 A Phase I study that showed that radiolabelled teneligliptin was excreted in almost exactly equal quantities in the feces and urine.
25. Halabi A, Maatouk H, Siegler KE, et al. Pharmacokinetics of teneligliptin in subjects with renal impairment. Clin Pharm Drug Dev 2013;2:246-54 • A study of teneligliptin in subjects with renal impairment. The results indicated that dose adjustment may not be needed when teneligliptin is used in subjects with mild, moderate or severe renal impairment.
26. Halabi A, Maatouk H, Siegler KE, et al. Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment. Clin Pharm Drug Dev 2014;3(4):290-6 • A study of teneligliptin in subjects with hepatic impairment. There were small increases in Cmax and AUC, but below the threshold for dose adjustment.
27. Kadowaki T, Kondo K. Efficacy, safety and dose-response relationship of teneligliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus. Diabetes Obes Metab 2013;15(9):810-18 •• A randomized controlled trial of teneligliptin in Japanese T2DM patients. The results showed clinically relevant HbA1c and FPG reductions, and that teneligliptin was generally well tolerated.
28. Kadowaki T, Kondo K. Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study with an open-label, long-term extension. Diabetes Obes Metab 2014;16(5):418-25
29. Kadowaki T, Kondo K. Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig 2013;4(6):576-84
30. Eto T, Inoue S, Kadowaki T. Effects of once-daily teneligliptin on 24-h blood glucose control and safety in Japanese patients with type 2 diabetes mellitus: a 4-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 2012;14(11):1040-6 •• A placebo-controlled trial of once-daily teneligliptin in Japanese T2DM patients that demonstrated that the postprandial glucose-lowering effects of teneligliptin administered before breakfast were sustained throughout the day.
31. Tanaka S, Suzuki I, Aoki C, et al. Add-on treatment with teneligliptin ameliorates glucose fluctuations and improves glycemic control index in Japanese patients with type 2 diabetes on insulin therapy. Diabetes Technol Ther 2014;16(12):840-5 •• A study showing that teneligliptin improves glucose fluctuations in combination with insulin therapy.
32. Tsuchimochi W, Ueno H, Yamashita E, et al. Teneligliptin improves glycemic control with the reduction of postprandial insulin requirement in Japanese diabetic patients. Endocr J 2014; doi: 10.1507/endocrj.EJ14-0393 •• A study showing that teneligliptin improves glucose fluctuations.
33. Otsuki H, Kosaka T, Nakamura K, et al. Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes. Int Urol Nephrol 2014;46(2):427-32
34. Nakagami H, Pang Z, Shimosato T, et al. The dipeptidyl peptidase-4 inhibitor teneligliptin improved endothelial dysfunction and insulin resistance in the SHR/NDmcr-cp rat model of metabolic syndrome. Hypertens Res 2014;37:629-35 •• A study in a rat model of metabolic syndrome. It was demonstrated that long-term treatment with teneligliptin significantly improved endothelial dysfunction and glucose metabolism in this model.
35. Takase B, Nagata M. Subacute effect of a novel dipeptidyl peptidase-4 inhibitor teneligliptin on endothelial function in humans. J N Remedies Clin 2013;50:698-704
36. Ceriello A. The post-prandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metab Res Rev 2000;16(2):125-32
37. Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother 2013;14(15):2047-58
38. Scheen AJ. A review of gliptins for 2014. Expert Opin Pharmacother 2014;10:1-20
39. Kubota T, Kubota N, Kumagai H, et al. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab 2011;13(3):294-307