Comparative review of dipeptidyl peptidase-4 inhibitors and sulphonylureas

Diabetes, Obesity and Metabolism

Volumn 18, Issue 4, 2016, Pages 333-347

  Deacon, C F ^a   Lebovitz, H E ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b SUNY DOWNSTATE MEDICAL CENTER   (United States)

Author keywords

Alogliptin; Anagliptin; Antidiabetic drug; Diabetes mellitus; Evogliptin; Gemigliptin; Glibenclamide; Gliclazide; Glimepiride; Glipizide; GLP 1; Glyburide; Glycaemic control; Incretin; Linagliptin; Omarigliptin; Saxagliptin; Sitagliptin; Teneligliptin; Trelagliptin; Vildagliptin

Indexed keywords

ALOGLIPTIN; ANAGLIPTIN; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EVOGLIPTIN; GEMIGLIPTIN; GLIBENCLAMIDE; GLICLAZIDE; GLIMEPIRIDE; GLIPIZIDE; HEMOGLOBIN A1C; LINAGLIPTIN; OMARIGLIPTIN; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA DERIVATIVE; TENELIGLIPTIN; TRELAGLIPTIN; VILDAGLIPTIN; ANTIDIABETIC AGENT; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN;

ACUTE CORONARY SYNDROME; BINDING AFFINITY; BODY WEIGHT DISORDER; BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ENZYME SPECIFICITY; GEOGRAPHIC DISTRIBUTION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; GLUCURONIDATION; GLYCEMIC CONTROL; HEART INFARCTION; HEMOGLOBIN BLOOD LEVEL; HOSPITALIZATION; HUMAN; HYPOGLYCEMIA; INSULIN RELEASE; ISCHEMIC PRECONDITIONING; KIDNEY FUNCTION; MEMBRANE DEPOLARIZATION; NON INSULIN DEPENDENT DIABETES MELLITUS; PHARMACODYNAMICS; REVIEW; STRUCTURE ACTIVITY RELATION; BLOOD; CARDIOVASCULAR DISEASES; CHEMICALLY INDUCED; COMPARATIVE STUDY; COMPLICATION; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DIABETIC CARDIOMYOPATHIES; DRUG EFFECTS; HYPERGLYCEMIA; ORAL DRUG ADMINISTRATION; RISK; WEIGHT GAIN;

ADMINISTRATION, ORAL; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DIABETIC CARDIOMYOPATHIES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; RISK; SULFONYLUREA COMPOUNDS; WEIGHT GAIN;

EID: 84959909719     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12610     Document Type: Review

References (153)

1. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995; 44: 1126-1131.
2. Deacon CF. Therapeutic strategies based on glucagon-like peptide 1. Diabetes 2004; 53: 2181-2189.
3. Deacon CF, Holst JJ. Pharmacology of GLP-1-based therapies. Review of Endocrinology 2008(January): 17-22.
4. Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes 1998; 47: 1663-1670.
5. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015; 58: 429-442.
6. Rodbard HW, Jellinger PS, Davidson JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009; 15: 540-559.
7. Garber AJ, Abrahamson MJ, Barzilay JI et al. American Association of Clinical Endocrinologists' comprehensive diabetes management algorithm 2013 consensus statement - executive summary. Endocr Pract 2013; 19: 536-557.
8. Latin American Diabetes Association. Treatment of type 2 diabetes in Latin America: Latin American Diabetes Association consensus statement. Available from URL: http://issuu.com/alad-diabetes/docs/guias_alad_2013. Accessed 31 July 2015.
9. Hopsu-Havu VK, Glenner GG. A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide. Histochemie 1966; 7: 197-201.
10. Mentlein R. Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul Pept 1999; 85: 9-24.
11. Augeri DJ, Robl JA, Betebenner DA et al. Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005; 48: 5025-5037.
12. Villhauer EB, Brinkman JA, Naderi GB et al. 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003; 46: 2774-2789.
13. Rasmussen HB, Branner S, Wiberg FC, Wagtmann N. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat Struct Biol 2003; 10: 19-25.
14. Abbott CA, Yu DM, Woollatt E, Sutherland GR, McCaughan GW, Gorrell MD. Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur J Biochem 2000; 267: 6140-6150.
15. Olsen C, Wagtmann N. Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV. Gene 2002; 299: 185-193.
16. Lankas GR, Leiting B, Roy RS et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 2005; 54: 2988-2994.
17. Burkey BF, Hoffmann PK, Hassiepen U, Trappe J, Juedes M, Foley JE. Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited. Diabetes Obes Metab 2008; 10: 1057-1061.
18. Feng J, Zhang Z, Wallace MB et al. Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J Med Chem 2007; 50: 2297-2300.
19. Kato N, Oka M, Murase T et al. Discovery and pharmacological characterization of N-[2-(2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl amino)-2-methylpropyl]-2-methylpyrazolo[1, 5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg Med Chem 2011; 19: 7221-7227.
20. Gu N, Park MK, Kim TE et al. Multiple-dose pharmacokinetics and pharmacodynamics of evogliptin (DA-1229), a novel dipeptidyl peptidase IV inhibitor, in healthy volunteers. Drug Des Devel Ther 2014; 8: 1709-1721.
21. Hwang DM, Kim SH. Kim et al. LC15-0444 is a novel, potent, selective, and orally active dipeptidyl peptidase IV inhibitor. Poster presented at the 68th American Diabetes Association Scientific Sessions, San Francisco, 2008; Poster 502-P. Available from URL: http://professional.diabetes.org/Content/Posters/2008/p502-P.pdf. Accessed 13 October 2015.
22. Eckhardt M, Langkopf E, Mark M et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3, 7-dihydropurine-2, 6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem 2007; 50: 6450-6453.
23. Biftu T, Sinha-Roy R, Chen P et al. Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J Med Chem 2014; 57: 3205-3212.
24. Kim D, Wang L, Beconi M et al. (2R)-4-oxo-4-[3-(trifluoromethyl)-5, 6-dihydro[1, 2, 4]triazolo[4, 3-a]pyrazin-7(8H)-yl]-1-(2, 4, 5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005; 48: 141-151.
25. 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: 5705-5719.
26. Lehrke M, Marx N, Patel S et al. Safety and tolerability of linagliptin in patients with type 2 diabetes: a comprehensive pooled analysis of 22 placebo-controlled studies. Clin Ther 2014; 36: 1130-1146.
27. Hirshberg B, Parker A, Edelberg H, Donovan M, Iqbal N. Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2014; 30: 556-569.
28. Engel SS, Round E, Golm GT, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther 2013; 4: 119-145.
29. Schweizer A, Dejager S, Foley JE, Kothny W. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies. Vasc Health Risk Manag 2011; 7: 49-57.
30. 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: 1061-1072.
31. 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: 1327-1335.
32. 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: 1317-1326.
33. Green JB, Bethel MA, Armstrong PW et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373: 232-242.
34. Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 2011; 13: 7-18.
35. McCormack PL. Evogliptin: first global approval. Drugs 2015; 75: 2045-2049.
36. Kim N, Patrick L, Mair S et al. Absorption, metabolism and excretion of [14C]gemigliptin, a novel dipeptidyl peptidase 4 inhibitor, in humans. Xenobiotica 2014; 44: 522-530.
37. 14C]omarigliptin, a once-weekly DPP-4 inhibitor, in humans. Poster presented at 74th American Diabetes Association Scientific Sessions, San Francisco, 2014; Poster 1080-P. Available from the ADA ePoster archives via URL: https://ada.scientificposters.com/epsSearchADA.cfm. Accessed 27 October 2015.
38. Nakamaru Y, Hayashi Y, Ikegawa R et al. Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin in humans. Xenobiotica 2014; 44: 242-253.
39. McKeage K. Trelagliptin: first global approval. Drugs 2015; 75: 1161-1164.
40. Furuta S, Smart C, Hackett A, Benning R, Warrington S. Pharmacokinetics and metabolism of [14C]anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in humans. Xenobiotica 2013; 43: 432-442.
41. Ahrén B, Schweizer A, Dejager S, Villhauer EB, Dunning BE, Foley JE. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes Metab 2011; 13: 775-783.
42. 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: 191-196.
43. Tatosian DA, Guo Y, Schaeffer AK et al. Dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes treated with saxagliptin, sitagliptin, or vildagliptin. Diabetes Ther 2013; 4: 431-442.
44. Noh YH, Lim HS, Jin SJ et al. Effects of ketoconazole and rifampicin on the pharmacokinetics of gemigliptin, a dipeptidyl peptidase-IV inhibitor: a crossover drug-drug interaction study in healthy male Korean volunteers. Clin Ther 2012; 34: 1182-1194.
45. Japanese Pharmaceuticals and Medical Devices Agency. Teneligliptin review report. Available from URL: http://www.pmda.go.jp/files/000153594.pdf. Accessed 30 July 2015.
46. Asakura M, Fujii H, Atsuda K, Itoh T, Fujiwara R. Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in human liver. Drug Metab Dispos 2015; 43: 477-484.
47. European Medicines Agency. Alogliptin; Summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002182/WC500152271.pdf. Accessed 30 July 2015.
48. Anagliptin; Prescribing information 2015. Available from URL: http://www.rad-ar.or.jp/siori/english/kekka_plain.cgi?n=32790. Accessed 30 July 2015.
49. European Medicines Agency. Linagliptin; Summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002110/WC500115745.pdf. Accessed 30 July 2015.
50. European Medicines Agency. Saxagliptin; Summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001039/WC500044316.pdf. Accessed 30 July 2015.
51. Omarigliptin; Japanese prescribing information 2015. Available from URl: https://www.msdconnect.jp/static/mcijapan/images/pi_marizev_tab.pdf. Accessed 27 October 2015.
52. European Medicines Agency. Sitagliptin; Summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000722/WC500039054.pdf. Accessed 30 July 2015.
53. Japanese Pharmaceuticals and Medical Devices Agency. Teneligliptin; Review report. Available from URL: http://www.pmda.go.jp/files/000153594.pdf. Accessed 30 July 2015.
54. Trelagliptin; Japanese prescribing information 2015. Available from URL: http://www.takedamed.com/content/medicine/pdf/zafatek.pdf. Accessed 30 July 2015.
55. European Medicines Agency. Vildagliptin; Summary of product characteristics. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf. Accessed 30 July 2015.
56. American Diabetes Association. Standards of medical care in diabetes - 2014. Diabetes Care 2014; 37(Suppl. 1): S14-S80.
57. Davis TM. Dipeptidyl peptidase-4 inhibitors: pharmacokinetics, efficacy, tolerability and safety in renal impairment. Diabetes Obes Metab 2014; 16: 891-899.
58. Boulton DW, Li L, Frevert EU et al. Influence of renal or hepatic impairment on the pharmacokinetics of saxagliptin. Clin Pharmacokinet 2011; 50: 253-265.
59. Graefe-Mody U, Rose P, Retlich S et al. Pharmacokinetics of linagliptin in subjects with hepatic impairment. Br J Clin Pharmacol 2012; 74: 75-85.
60. Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. 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.
61. Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther 2014; 5: 1-41.
62. Jin SM, Park SW, Yoon KH et al. Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension. Diabetes Obes Metab 2015; 17: 511-515.
63. Rhee EJ, Lee WY, Min KW et al. 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: 523-530.
64. Scheen AJ, Charpentier G, Ostgren CJ, Hellqvist A, Gause-Nilsson I. 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: 540-549.
65. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications 2010; 24: 79-83.
66. Guerci B, Monnier L, Serusclat P et al. Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized Optima study. Diabetes Metab 2012; 38: 359-366.
67. Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care 2012; 35: 2076-2082.
68. Kothny W, Lukashevich V, Foley JE, Rendell MS, Schweizer A. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial. Diabetologia 2015; 58: 2020-2026.
69. Inagaki N, Onouchi H, Maezawa H, Kuroda S, Kaku K. Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: a randomised, double-blind, phase 3, non-inferiority study. Lancet Diabetes Endocrinol 2015; 3: 191-197.
70. Gantz I, Okamoto T, Ito Y, Okuyama K, Engel SS. Effect of omarigliptin, a novel once-weekly DPP-4 inhibitor, in Japanese patients with type 2 diabetes: a placebo- and sitagliptin-controlled trial. Diabetologia 2014; 57(Suppl. 1): S55 (Abstract 115).
71. Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother 2013; 14: 2047-2058.
72. Egan AG, Blind E, Dunder K et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N Engl J Med 2014; 370: 794-797.
73. ADA/EASD/IDF recommendations for clinicians and people with diabetes concerning the use of incretin therapy and pancreatic disease. Available from URL: http://easd.org/index.php?option=com_content&view=article&id=172. Accessed 6 March 2015.
74. Raz I, Bhatt DL, Hirshberg B et al. Incidence of pancreatitis and pancreatic cancer in a randomized controlled multicenter trial (SAVOR-TIMI 53) of the dipeptidyl peptidase-4 inhibitor saxagliptin. Diabetes Care 2014; 37: 2435-2441.
75. Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 2014; 57: 1320-1324.
76. Karagiannis T, Boura P, Tsapas A. Safety of dipeptidyl peptidase 4 inhibitors: a perspective review. Ther Adv Drug Saf 2014; 5: 138-146.
77. Scirica BM, Braunwald E, Raz I et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 2014; 130: 1579-1588.
78. Zannad F, Cannon CP, Cushman WC et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015; 385: 2067-2076.
79. Loubatieres A. The mechanism of action of the hypoglycemic sulfonamides; a concept based on investigations in animals and in man. Diabetes 1957; 6: 408-417.
80. Lebovitz HE, Melander A. Sulfonylureas and Meglinides: insights into physiology and translational clinical utility. In: DeFronzo RA, Alberti KGGM, Ferrannini E, Zimmet P, eds. International Textbook of Diabetes Mellitus. 4th edn. Chichester: John Wiley and Sons, 2015; 615-640.
81. Inagaki N, Gonoi T, Clement JP IV et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 1995; 270: 1166-1170.
82. Aittoniemi J, Fotinou C, Craig TJ, de Wet H, Proks P, Ashcroft FM. SUR1: a unique ATP binding cassette protein functions as an ion channel regulator. Philos Trans R Soc B: Biol Sci 2009; 364: 257-267.
83. Gribble FM, Tucker SJ, Seino S, Ashcroft FM. Tissue specificity of sulfonylureas. Studies on cloned cardiac and β-cell KATP channels. Diabetes 1998; 47: 1412-1418.
84. Seino S, Takahashi H, Takahashi T, Shibasaki T. Treating diabetes today: a matter of selectivity of sulphonylureas. Diabetes Obes Metab 2012; 14(Suppl. 1): 9-13.
85. Winkler M, Stephen D, Bieger S, Kuhner P, Wolff F, Quest U. Testing the bipartite model of the sulfonylurea receptor binding site: binding of A-, B-, and A + B-site ligands. J Pharmacol Exp Ther 2007; 322: 701-708.
86. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005; 65: 385-411.
87. Electronic Medicines Compendium (eMC). Glibenclamide; Summary of product characteristics. Available from URL: http://www.medicines.org.uk/emc/medicine/30411. Accessed 30 July 2015.
88. Electronic Medicines Compendium (eMC). Gliclazide; Summary of product characteristics. Available from URL: http://www.medicines.org.uk/emc/medicine/25838. Accessed 30 July 2015.
89. Electronic Medicines Compendium (eMC). Glimepiride; Summary of product characteristics. Available from URL: http://www.medicines.org.uk/emc/medicine/25845. Accessed 30 July 2015.
90. Electronic Medicines Compendium (eMC). Glipizide; Summary of product characteristics. Available from URL: http://www.medicines.org.uk/emc/medicine/9851. Accessed 30 July 2015.
91. Abdelmoneim AS, Hasenbank SE, Seubert JM, Brocks DR, Light PE, Simpson SH. Variations in tissue selectivity amongst insulin secretagogues: a systematic review. Diabetes Obes Metab 2012; 14: 130-138.
92. Monami M, Dicembrini I, Kundisova L, Zannoni S, Nreu B, Mannucci E. A meta-analysis of the hypoglycaemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes. Diabetes Obes Metab 2014; 16: 833-840.
93. Holstein A, Plaschke A, Egberts EH. Lower incidence of severe hypoglycaemia in patients with type 2 diabetes treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev 2001; 17: 467-473.
94. Gangji AS1, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care 2007; 30: 389-394.
95. Schopman JE, Simon AC, Hoefnagel SJ, Hoekstra JB, Scholten RJ, Holleman F. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014; 30: 11-22.
96. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365: 2002-2012.
97. Farmer AJ, Brockbank KJ, Keech ML, England EJ, Deakin CD. Incidence and costs of severe hypoglycemia requiring attendance by the emergency medical services in South Central England. Diabet Med 2012; 29: 1447-1450.
98. Stahn A, Pistrosch F, Ganz X et al. Relationship between hypoglycemic episodes and ventricular arrhythmias in patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias and silent arrhythmias. Diabetes Care 2014; 37: 516-520.
99. Chow E, Bernjak A, Williams S et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes 2014; 63: 1738-1747.
100. Zoungas S, Patel A, Chalmers J et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363: 1410-1418.
101. Meier JJ, Gallwitz B, Schmidt WE, Mugge A, Nauck MA. Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important? Heart 2004; 90: 9-12.
102. Abdelmoneim AS, Eurich DT, Light PE et al. Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer. Diabetes Obes Metab 2015; 17: 523-532.
103. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853.
104. Roumie CL, Hung AM, Greevy RA et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med 2012; 157: 601-610.
105. Phung OJ, Schwartzman E, Allen RW, Engel SS, Rajpathak SN. Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis. Diabet Med 2013; 30: 1160-1171.
106. Morgan CL, Mukherjee J, Jenkins-Jones S, Holden SE, Currie CJ. Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study. Diabetes Obes Metab 2014; 16: 957-962.
107. Hong J, Zhang Y, Lai S et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 2013; 36: 1304-1311.
108. Lee T-M, Chou T-F. Impairment of myocardial protection in type 2 diabetic patients. J Clin Endocrinol Metab 2003; 88: 531-537.
109. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008; 88: 581-609.
110. Schramm TK, Gislason GH, Vaag A et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J 2011; 32: 1900-1908.
111. Mogensen UM, Andersson C, Fosbøl EL et al. Metformin in combination with various insulin secretagogues in type 2 diabetes and associated risk of cardiovascular morbidity and mortality-A retrospective nationwide study. Diabetes Res Clin Pract 2015; 107: 104-112.
112. Simpson SH, Lee J, Choi S, Vandermeer B, Abdelmoneim AS, Featherstone TR. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Lancet Diabetes Endocrinol 2015; 3: 43-51.
113. Nathan DM. Finding new treatments for diabetes - how many, how fast... how good? N Engl J Med 2007; 356: 437-440.
114. Bloomgarden ZT, Inzucchi SE. New treatments for diabetes. N Engl J Med 2007; 356: 2219-2220.
115. Seck T, Nauck M, Sheng D et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study. Int J Clin Pract 2010; 64: 562-576.
116. Filozof C, Gautier JF. A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized study. Diabet Med 2010; 27: 318-326.
117. Gallwitz B, Rosenstock J, Rauch T et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012; 380: 475-483.
118. Derosa G, Cicero AF, Franzetti IG et al. A randomized, double-blind, comparative therapy evaluating sitagliptin versus glibenclamide in type 2 diabetes patients already treated with pioglitazone and metformin: a 3-year study. Diabetes Technol Ther 2013; 15: 214-222.
119. Nauck MA1, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007; 9: 194-205.
120. 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: 1049-1058.
121. Krobot KJ, Ferrante SA, Davies MJ et al. Lower risk of hypoglycemia with sitagliptin compared to glipizide when either is added to metformin therapy: a pre-specified analysis adjusting for the most recently measured HbA(1c) value. Curr Med Res Opin 2012; 28: 1281-1287.
122. Ahrén B, Foley JE, Dejager S et al. Higher risk of hypoglycemia with glimepiride versus vildagliptin in patients with type 2 diabetes is not driven by high doses of glimepiride: divergent patient susceptibilities? Diabetes Ther 2014; 5: 459-469.
123. Gallwitz B, Rosenstock J, Patel S et al. Regardless of the degree of glycaemic control, linagliptin has lower hypoglycaemia risk than all doses of glimepiride, at all time points, over the course of a 2-year trial. Diabetes Obes Metab 2015; 17: 276-284.
124. Gitt AK1, Bramlage P, Binz C, Krekler M, Deeg E, Tschöpe D. Prognostic implications of DPP-4 inhibitor vs. sulfonylurea use on top of metformin in a real world setting - results of the 1 year follow-up of the prospective DiaRegis registry. Int J Clin Pract 2013; 67: 1005-1014.
125. Abbatecola AM, Paolisso G, Sinclair AJ. Treating diabetes mellitus in older and oldest old patients. Curr Pharm Des 2015; 21: 1665-1671.
126. Avogaro A, Dardano A, de Kreutzenberg SV, Del Prato S. Dipeptidyl peptidase-4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes. Diabetes Obes Metab 2015; 17: 107-115.
127. Hartley P, Shentu Y, Betz-Schiff P et al. Efficacy and tolerability of sitagliptin compared with glimepiride in elderly patients with type 2 diabetes mellitus and inadequate glycemic control: a randomized, double-blind, non-inferiority trial. Drugs Aging 2015; 32: 469-476.
128. Schernthaner G, Durán-Garcia S, Hanefeld M et al. Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION). Diabetes Obes Metab 2015; 17: 630-638.
129. Turner RC, Holman RR, Matthews DR. Sulfonylurea failure and inadequacy. In: Cameron D, Colagiuri S, Heding L, et al., eds. Non-Insulin-Dependent Diabetes Mellitus. Hong Kong: Excerpta Medica, 1989; 52-56.
130. Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-2443.
131. Leibowitz G, Cahn A, Bhatt DL et al. Impact of treatment with saxagliptin on glycaemic stability and β-cell function in the SAVOR-TIMI 53 study. Diabetes Obes Metab 2015; 17: 487-494.
132. Valensi P, de Pouvourville G, Benard N et al. Treatment maintenance duration of dual therapy with metformin and sitagliptin in type 2 diabetes: The ODYSSEE observational study. Diabetes Metab 2015; 41: 231-238.
133. Inzucchi SE, Tunceli K, Qiu Y et al. Progression to insulin therapy among type 2 diabetes patients treated with sitagliptin or sulfonylurea plus metformin dual therapy. Diabetes Obes Metab 2015; 17: 956-964.
134. Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013; 15: 938-953.
135. Morgan CL, Mukherjee J, Jenkins-Jones S, Holden SE, Currie CJ. Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes Obes Metab 2014; 16: 977-983.
136. Yu OH, Yin H, Azoulay L. The combination of DPP-4 inhibitors versus sulfonylureas with metformin after failure of first-line treatment in the risk for major cardiovascular events and death. Can J Diabetes 2015; 39: 383-389.
137. Seong JM, Choi NK, Shin JY et al. Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study. PLoS One 2015; 10: e0124287.
138. ®). Diab Vasc Dis Res 2015; 12: 164-174.
139. Hermansen K, Kipnis M, Luo E, Fanvrik D, KhatAmi H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabeytes mellitus inadequately controlled on glimepiride or on glimepiride and metformin. Diabetes Obes Metab 2007; 9: 733-745.
140. Ahrén B, Schweizer A, Dejager S et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab 2009; 94: 1236-1243.
141. Solis-Herrera C, Triplitt C, Garduno-Garcia Jde J, Adams J, DeFronzo RA, Cersosimo E. Mechanisms of glucose lowering of dipeptidyl peptidase-4 inhibitor sitagliptin when used alone or with metformin in type 2 diabetes: a double-tracer study. Diabetes Care 2013; 36: 2756-2762.
142. Szoke E, Gosmanov NR, Sinkin JC et al. Effects of glimepiride and glyburide on glucose counterregulation and recovery from hypoglycemia. Metabolism 2006; 55: 78-83.
143. Cooperberg BA, Cryer PE. Beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans. Diabetes Care 2009; 32: 2275-2280.
144. Vardarli I, Arndt E, Deacon CF, Holst JJ, Nauck MA. Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and "isoglycemic" intravenous glucose. Diabetes 2014; 63: 663-674.
145. Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care 2007; 30: 1979-1987.
146. Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA 2010; 303: 1410-1418.
147. Pearson ER, Flechtner I, Njolstad PR et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006; 355: 467-477.
148. Pearson ER, Liddle WG, Shepherd M, Corrall RJ, Hattersley AT. Sensitivity to sulphonylureas in patients with hepatic nuclear factor (HNF)-1 alpha gene mutations: evidence for pharmacogenetics in diabetes. Diabet Med 2000; 17: 543-545.
149. Pearson ER, Donnelly LA, Kimber C et al. Variation in TCF7L2 influences therapeutic response to sulfonylureas. A GoDARTs study. Diabetes 2007; 56: 2178-2182.
150. Bowman P, Flanagan SE, Edghill EL et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012; 55: 123-127.
151. Javorsky M1, Klimcakova L, Schroner Z et al. KCNJ11 gene E23K variant and therapeutic response to sulfonylureas. Eur J Intern Med 2012; 23: 245-249.
152. Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet 2010; 49: 573-588.
153. Nathan DM, Buse JB, Kahn SE et al. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care 2013; 36: 2254-2261.