Emerging gliptins for type 2 diabetes

Expert Opinion on Emerging Drugs

Volumn 18, Issue 2, 2013, Pages 245-258

  Cahn, Avivit ^a   Raz, Itamar ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Aloglitpin; Anagliptin; DPP 4 inhibitor; Evogliptin; Gemigliptin; Gosogliptin; Linagliptin; Melogliptin; Omarigliptin; Saxagliptin; Sitagliptin; Teneligliptin; Trelagliptin; Vildagliptin

Indexed keywords

ALOGLIPTIN; ANAGLIPTIN; DA 1229; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EVOGLIPTIN; EXENDIN 4; GEMIGLIPTIN; GLUCAGON LIKE PEPTIDE 1; GOSOGLIPTIN; INCRETIN; LINAGLIPTIN; MELOGLIPTIN; METFORMIN; OMARIGLIPTIN; PIOGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; TENELIGLIPTIN; TRELAGLIPTIN; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ANTIDIABETIC ACTIVITY; AREA UNDER THE CURVE; CALORIC INTAKE; CARBOHYDRATE METABOLISM; CELL SURVIVAL; DIARRHEA; DRUG COST; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MARKETING; DRUG SAFETY; DRUG TOLERABILITY; GASTROINTESTINAL SYMPTOM; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; INSULIN RELEASE; LIFESTYLE MODIFICATION; MONOTHERAPY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PATIENT COMPLIANCE; POLYPHARMACY; REVIEW; STOMACH EMPTYING; VOMITING;

ANIMALS; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HUMANS;

EID: 84878556491     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2013.807796     Document Type: Review

References (96)

1. IDF Diabetes Atlas update. 2012.Available from: http://www.idf.org/ diabetesatlas/5e/Update2012 [Last accessed 14 March 2013]
2. IDF Diabetes Atlas. Available from: http://www.idf.org/diabetesatlas/5e/ the-global-burden [last accessed 14 March 2013]
3. Inzucchi SE, Bergenstal RM, Buse JB, et al. American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364-79
4. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 2011;154:602-13
5. Elrick H, Stimmler L, Hlad CJ Jr, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964;24:1076-82
6. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-57
7. Russell-Jones D, Gough S. Recent advances in incretin-based therapies. Clin Endocrinol (Oxf) 2012;77:489-99
8. Vilsbøll T. The effects of glucagon-like peptide-1 on the beta cell. Diabetes Obes Metab 2009;11(Suppl 3):11-18
9. Boonacker E, Van Noorden CJ. The multifunctional or moonlighting protein CD26/DPPIV. Eur J Cell Biol 2003;82:53-73
10. Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986;29:46-52
11. Nauck MA, Kleine N, Orskov C, et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741-4
12. Davidson JA. Incorporating incretin-based therapies into clinical practice: differences between glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. Mayo Clin Proc 2010;85(12 Suppl):S27-37
13. DeFronzo RA, Okerson T, Viswanathan P, et al. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin 2008;24:2943-52
14. Bergenstal RM, Wysham C, Macconell L, et al. DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010;376:431-9
15. Scheen AJ. A review of gliptins in 2011. Expert Opin Pharmacother 2012;13:81-99
16. Karagiannis T, Paschos P, Paletas K, et al. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ 2012;344:e1369
17. Morgan CL, Poole CD, Evans M, et al. What next after metformin? A retrospective evaluation of the outcome of second-line, glucose-lowering therapies in people with type 2 diabetes. J Clin Endocrinol Metab 2012;97:4605-12
18. Datamonitor Healthcare's Diabetes Hot Topics. Use of key non-insulin brands in the type 2 diabetes treatment algorithm. Henry C. 27 April 2012. Reference Code DMKC0053693
19. Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care 2004;27:1218-24
20. Polonsky WH, Fisher L, Hessler D, et al. Patient perspectives on once-weekly medications for diabetes. Diabetes Obes Metab 2011;13:144-9
21. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-28
22. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-44
23. Skyler JS, Bergenstal R, Bonow RO, et al. American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VADT Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol 2009;53:298-304
24. Woodcock J, Sharfstein JM, Hamburg M. Regulatory action on rosiglitazone by the U.S. Food and Drug Administration. N Engl J Med 2010;363:1489-91
25. Scirica BM, Bhatt DL, Braunwald E, et al. The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. Am Heart J 2011;162:818-25
26. Leahy JL, Hirsch IB, Peterson KA, Schneider D. Targeting beta-cell function early in the course of therapy for type 2 diabetes mellitus. J Clin Endocrinol Metab 2010;95:4206-16
27. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med 2010;363:2339-50
28. Viereck C, Boudes P. An analysis of the impact of FDA's guidelines for addressing cardiovascular risk of drugs for type 2 diabetes on clinical development. Contemp Clin Trials 2011;32:324-32
29. Available from: http://www.novartis.com/downloads/newsroom/corporate- fact-sheet/2a-Pharmaceuticals-EN.pdf [Last accessed 10 May 2013]
30. Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs 2011;71:1441-67
31. Furuta S, Smart C, Hackett A, et al. Pharmacokinetics and metabolism of [(14)C]anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in humans. Xenobiotica 2013;43:432-42
32. Sunami Y, Yoshioka N, Hayashi I, Ishida T. Safety, tolerability, pharmacokinetics and pharmacodynamics of SK-0403, a novel DPP-IV inhibitor, in healthy Japanese subjects [abstract 0482-P]. 67th Meet Am Diabetes Assoc; Chicago; 2007
33. Suiny drug information sheet. Available from: http://www.rad-ar.or.jp/ siori/english/kekka.cgi?n=32790 [Last accessed 13 March 2013]
34. Lim KS, Cho JY, Kim BH, et al. Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers. Br J Clin Pharmacol 2009;68:883-90
35. 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;696:194-202
36. 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;14:1040-6
37. 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;published online 6 Mar 2013; doi: 10.1111/dom.12092
38. Rosenstock J, Rendell MS, Gross JL, et al. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab 2009;11:1145-52
39. Vilsbøll T, Rosenstock J, Yki-Järvinen H, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:167-77
40. Barnett AH, Charbonnel B, Donovan M, et al. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin 2012;28:513-23
41. Hong ES, Khang AR, Yoon JW, et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab 2012;14:795-802
42. Kothny W, Foley J, Kozlovski P, et al. Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2013;15:252-7
43. Available from: www.clinicaltrials.gov trial no NCT00954447
44. Rhee EJ, Lee WY, Min KW, et al. Gemigliptin Study 006 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor gemigliptin compared with sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Obes Metab 2013;15:523-30
45. Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2010;20:224-35
46. Scheen AJ, Charpentier G, Ostgren CJ, et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2010;26:540-9
47. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33:187-215 • A thorough review of the possible pleiotropic effects of the incretin system.
48. Chrysant SG, Chrysant GS. Clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase-4 inhibitors. Am J Cardiol 2012;109:1681-5
49. Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4 inhibitors. Diab Vasc Dis Res 2012;9:109-16
50. Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin 2011;27(Suppl 3):57-64 •• The authors review 53 clinical trials with DPP-4 inhibitors and assess the effect of these drugs on the incidence of major cardiovascular events, cancer and pancreatitis.
51. van Genugten RE, van Raalte DH, Diamant M. Dipeptidyl peptidase-4 inhibitors and preservation of pancreatic islet-cell function: a critical appraisal of the evidence. Diabetes Obes Metab 2012;14:101-11
52. Richard KR, Shelburne JS, Kirk JK. Tolerability of dipeptidyl peptidase-4 inhibitors: a review. Clin Ther 2011;33:1609-29
53. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007;298:194-206
54. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008;2):CD006739
55. Willemen MJ, Mantel-Teeuwisse AK, Straus SM, et al. Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionality analysis in the World Health Organization VigiBase. Diabetes Care 2011;34:369-74
56. Gooßen K, Gräber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2012;14:1061-72
57. Park H, Park C, Kim Y, Rascati KL. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother 2012;46:1453-69
58. Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150-6
59. Cure P, Pileggi A, Alejandro R. Exenatide and rare adverse events. N Engl J Med 2008;358(18):1969-72
60. Scheen A. Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf 2013;Epub ahead of print
61. Singh S, Chang HY, Richards TM, et al. Glucagon-like Peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013;173:534-9
62. Engel SS, Williams-Herman DE, Golm GT, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract 2010;64:984-90
63. Ligueros-Saylan M, Foley JE, Schweizer A, et al. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab 2010;12:495-509
64. Eurich DT, Simpson S, Senthilselvan A, et al. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ 2013;346:f2267
65. Available from: Error! Hyperlink reference not valid.-Error! Hyperlink reference not valid. NCT01243424, NCT01107886, NCT00790205, NCT00894868, NCT00968708 [Last accessed 13 March 2013]
66. American Diabetes Association. Economic costs of diabetes in the U.S. In 2007. Diabetes Care 2008;31:596-615
67. Novartis group annual report. 2012.Available from: http://www.novartis. com/downloads/investors/reports/annual-report-2012-financial-report-en. pdf [Last accessed 13 March 2013]
68. AstraZeneca PLC Fourth quarter and full year results. 2012. Available from: http://www.astrazeneca.com/Media/Press-releases/Article/20130131- astrazeneca-2012-fourth-quarter-and-full-year-results [Last accessed 13 March 2013]
69. Merck Announces Full-Year and Fourth-Quarter 2012 Financial Results. Available from: http://www.merck.com/investors/financials/4Q12SERelease-01-02- 2013.pdf [Last accessed 13 March 2013]
70. Takeda Pharmaceutical Co. Ltd. Sales of major products. Available from: http://www.takeda.com/investor-information/highlights/products.html [Last accessed 13 March 2013]
71. Marguet D, Baggio L, Kobayashi T, et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 2000;97:6874-9
72. Nagakura T, Yasuda N, Yamazaki K, et al. Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochem Biophys Res Commun 2001;284:501-6
73. Hansotia T, Baggio LL, Delmeire D, et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes 2004;53:1326-35
74. Kos K, Baker AR, Jernas M, et al. DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue. Diabetes Obes Metab 2009;11:285-92
75. Aaboe K, Knop FK, Vilsbøll T, et al. Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2010;12:323-33
76. Fadini GP, Boscaro E, Albiero M, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care 2010;33:1607-9
77. Theiss HD, Brenner C. Engelmann et al. Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in patients suffering from Acute Myocardial Infarction (SITAGRAMI-Trial)-rationale, design and first interim analysis. Int J Cardiol 2010;145:282-4
78. Monami M, Lamanna C, Desideri CM, Mannucci E. DPP-4 inhibitors and lipids: systematic review and meta-analysis. Adv Ther 2012;29:14-25
79. Brown NJ. Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. J Am Soc Hypertens 2012;6:163-8
80. Mistry GC, Maes AL, Lasseter KC, et al. Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension. J Clin Pharmacol 2008;48:592-8
81. Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans. Hypertension 2010;56:728-33
82. Pharmaprojects-copyright to Citeline Drug Intelligence (an informa business) search results: evogliptin, melogliptin, gosogliptin, omargliptin, trelagliptin
83. Gantz I, Chen M, Mirza A, et al. Effect of MK-3102, a novel once-weekly DPP-4 inhibitor, over 12 weeks in patients with type 2 diabetes mellitus [Presentation no. 110]. 48th EASD Annual Meeting; Berlin; 2012
84. TODAY Study Group. Zeitler P, Hirst K, Pyle L, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012;366:2247-56
85. Available from: Error! Hyperlink reference not valid. NCT00730275, NCT00957268, NCT01342484, NCT01525225
86. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care 2012;35:2650-64
87. Pratley RE, Rosenstock J, Pi-Sunyer FX, et al. Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care 2007;30:3017-22
88. Barzilai N, Guo H, Mahoney EM, et al. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin 2011;27:1049-58
89. Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care 2011;34:1463-8
90. Rother KI, Spain LM, Wesley RA, et al. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care 2009;32:2251-7
91. Varanasi A, Bellini N, Rawal D, et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol 2011;165:77-84
92. Garg SK, Moser EG, Bode BW, et al. Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial. Endocr Pract 2013;19:19-28
93. Farngren J, Persson M, Schweizer A, et al. Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon counterregulation during hypoglycemia in type 1 diabetes. J Clin Endocrinol Metab 2012;97:3799-806
94. Available from: Error! Hyperlink reference not valid. NCT01155284
95. 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
96. Thrasher J, Daniels K, Patel S, Whetteckey J. Black/African American patients with type 2 diabetes mellitus: study design and baseline patient characteristics from a randomized clinical trial of linagliptin. Expert Opin Pharmacother 2012;13:2443-52