Potential cardiovascular effects of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Current evidence and ongoing trials

European Heart Journal, Supplement

Volumn 14, Issue SUPPL. B, 2012, Pages

  Mosenzon, Ofri ^a   Raz, Itamar ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Cardiovascular disease; Dipeptidyl peptidase 4 (DPP 4) inhibitors; Guidelines; Type 2 diabetes mellitus

Indexed keywords

ACARBOSE; ALOGLIPTIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLIBENCLAMIDE; GLICLAZIDE; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON LIKE PEPTIDE 1; INCRETIN; INSULIN; LINAGLIPTIN; METFORMIN; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN; VOGLIBOSE;

ACUTE CORONARY SYNDROME; ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; DIABETIC PATIENT; DRUG APPROVAL; DRUG EFFICACY; DRUG SAFETY; FOOD INTAKE; GLUCOSE HOMEOSTASIS; HEART INFARCTION; HEART PROTECTION; HUMAN; META ANALYSIS (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PRACTICE GUIDELINE; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETROSPECTIVE STUDY; RISK ASSESSMENT; TRANSIENT ISCHEMIC ATTACK; TREATMENT DURATION;

EID: 84869167320     PISSN: 1520765X     EISSN: 15542815     Source Type: Journal    
DOI: 10.1093/eurheartj/sus003     Document Type: Article

References (56)

1. American Diabetes Association. Diabetes Statistics. http://www.diabetes. org/diabetes-basics/diabetes-statistics/(accessed 4 January 2012).
2. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD. VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139.
3. Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 2001;44(Suppl 2):S14-S21. (Pubitemid 32844108)
4. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
5. Wagenknecht LE, Zaccaro D, Espeland MA, Karter AJ, O'Leary DH, Haffner SM. Diabetes and progression of carotid atherosclerosis: the insulin resistance atherosclerosis study. Arterioscler Thromb Vasc Biol 2003;23:1035-1041. (Pubitemid 36713557)
6. Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care 2011;34(Suppl 2):S285-S290.
7. Nathanson D, Nyström T. Hypoglycemic pharmacological treatment of type 2 diabetes: targeting the endothelium. Mol Cell Endocrinol 2009;297:112-126.
8. Xu J, Zou MH. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation 2009;120:1266-1286.
9. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Price DL, Chen R, Udell J, Raz I. 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;162:818-825.
10. Holman RR, Paul SK, Bethel A, Matthews DR, Neil HAW. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589.
11. Control Group, Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, Evans GW, Gerstein HC, Holman RR, Moritz TE, Neal BC, Ninomiya T, Patel AA, Paul SK, Travert F, Woodward M. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288-2298.
12. Mannucci E, Monami M, Lamanna C, Gori F, Marchionni N. Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovas Dis 2009;19:604-612.
13. Ray KK, Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D, Erqou S, Sattar N. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes melli-tus: a meta-analysis of randomised controlled trials. Lancet 2009; 373:1765-1772.
14. ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364:818-828.
15. 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.
16. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356:2457-2471. (Pubitemid 46919772)
17. Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, Hughes RI, Khunti K, Wilkins MR, Majeed A, Elliott P. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009;339:b4731. doi:10.1136/bmj.b4731.
18. Food and Drug Administration: Guidance for Industry. Diabetes Mellitus-Evaluation Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes. 2008. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf.
19. European Medicines Agency. Guideline on Clinical Investigation of Medicinal Products in the Treatment of Diabetes Mellitus. January 2010. http://www.emea.europa.eu/docs/en-GB/document-library/Scientific-guideline/2010/ 02/WC500073570.pdf (accessed 12 January 2012).
20. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33:187-215.
21. Hirshberg B, Raz I. Impact of the U.S. Food and Drug Administration cardiovascular assessment requirements on the development of novel antidiabetes drugs. Diabetes Care 2011;34(Suppl 2):S101-S106.
22. Eichler HG, Oye K, Baird LG, Abadie E, Brown J, Drum CL, Ferguson J, Garner S, Honig P, Hukkelhoven M, Lim JC, Lim R, Lumpkin MM, Neil G, O'Rourke B, Pezalla E, Shoda D, Seyfert-Margolis V, Sigal EV, Sobotka J, Tan D, Unger TF, Hirsch G. Adaptive licensing: taking the next step in the evolution of drug approval. Clin Pharmacol Ther 2012;91:426-437.
23. Drucker JD, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696-1705. (Pubitemid 46048557)
24. AACE/ACE Summary of Key Benefits and Risks of Medications. https://www.aace.com/files/glycemic-control-algorithm-ppt.pdf (accessed 12 January 2012).
25. Cobble ME, Frederich R. Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data. Cardiovasc Diabetol 2012;11:6.
26. Schernthaner G, Barnett AH, Emser A, Patel S, Troost J, Woerle HJ, von Eynatten M. Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus. Diabetes Obes Metab 2012;14:470-8.
27. Ahrén B. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care 2007;30:1344-1350. (Pubitemid 46871136)
28. Ban K, Noyan-Ashraf H, Hoefer J, Bolz S-S, Drucker DJ, Husain M. Car-dioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and-ndependent pathways. Circulation 2008; 117:2340-2350. (Pubitemid 351653542)
29. Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005;54:146-151. (Pubitemid 40105106)
30. Bose AK, Mocanu MM, Carr RD, Yellon DM. Glucagon like peptide-1 is protective against myocardial ischemia/reperfusion injury when given either as a preconditioning mimetic or at reperfusion in an isolated rat heart model. Cardiovasc Drugs Ther 2005;19:9-11. (Pubitemid 40767767)
31. Huisamen B, Genis A, Marais E, Lochner A. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats. Cardiovasc Drugs Ther 2011;25:13-20.
32. Nikolaidis LA, Doverspike A, Hentosz T, Zourelias L, Shen Y-T, Elahi D, Shannon RP. Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 2005;312:303-308. (Pubitemid 40096482)
33. Poornima I, Bown SB, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP. Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive, heart failure-prone rat. Circ Heart Fail 2008;1:153-160.
34. Timmers L, Henriques JPS, de Kleijn DPV, D Vries JH, Kemperman H, Steendijk P, Verlaan WJ, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 2009;53:501-510.
35. Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima I, Shen Y-T, Shannon RP. Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. J Pharmacol Exp Ther 2006;317:1106-1113. (Pubitemid 43764114)
36. Halbirk M, Nørrelund H, Møller N, Holst JJ, Schmitz O, Nielsen R, Nielsen-Kudsk JE, Nielsen SS, Nielsen TT, Eiskjær H, Bøtker HE, Wiggers H. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol 2010;298:H1096-H1102.
37. Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004;109:962-965. (Pubitemid 38282847)
38. Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP. Glucagon-like peptide-1 infusion improves left ventricular ejection faction and functional status in patient with chronic heart failure. J Cardiac Fail 2006;12:694-699. (Pubitemid 44881367)
39. 2+ currents via activation of the cAMP-dependent protein kinase A pathway. Cardiovasc Diabetol 2011;10:6-14.
40. Hausenloy DJ, Yellon DM. New directions for protecting against is-chaemia-reperfusion injury: targeting the reperfusion injury salvage kinase (RISK)-pathway. Cardiovasc Res 2004;61:448-460. (Pubitemid 38210151)
41. White WB, Gorelick PB, Fleck P, Smith N, Wilson C, Pratley R. Cardiovascular events in patients receiving alogliptin: a pooled analysis of randomized clinical trials. In:70th Scientific Sessions of the American Diabetes Association, Orlando, FL, 2010. Abstract 391-PP.
42. Johansen OE, Eubacher N, Von Eynatten M, Patel S, Woerle HJ. Cardiovascular risk with linagliptin in patients with type 2 diabetes: a pre-specified, prospective, and adjudicated meta-analysis from a large phase III program. Cardiovasc Diabetol 2012;11:3.
43. Frederich R, Alexander JH, Fiedorek FT, Donovan M, Berglind N, Harris S, Chen R, Wolf R, Mahaffey KW. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes mellitus. Postgrad Med 2010;122:16-27.
44. Williams-Herman D, Engel SS, Round E, Johnson J, Golm GT, Guo H, Musser BJ, Davies MJ, Kaufman KD, Goldstein BJ. Safety and toler-ability of sitagliptin in clinical studies: a pooled analysis of data from 10, 246 patients with type 2 diabetes. BMC Endocr Disord 2010;10:7.
45. Schweizer A, Dejager S, Foley JE, Couturier A, Ligueros-Saylan M, Kothny W. Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events form a large phase III type 2 diabetes population. Diabetes Obes Metab 2010;12:485-494.
46. 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.
47. The Sentinel Initiative. May 2008. http://www.fda.gov/downloads/Safety/ FDAsSentinelInitiative/UCM124701.pdf (accessed 10 January 2012).
48. Behrman RE, Benner JS, Brown JS, McClellan M, Woodcock J, Platt R. Developing the sentinel system-a national resource for evidence development. N Engl J Med 2011;364:498-499.
49. FDA's Sentinel Initiative-Background. http://www.fda.gov/Safety/ FDAsSentinelInitiative/ucm149340.htm. (accessed 10 January 2012).
50. Selby J, Fireman B, Butler M. Report to FDA on a protocol for active surveillance of acute myocardial infarction in association with use of a pharmaceutical agent. 26 October 2010. http://www.mini-sentinel. org/work-products/Assessments/
51. AMI-Surveillance-Protocol-and-Appendices-ABC.pdf (accessed 10 January 2012).
52. White WB, Bakris GL, Bergenstal RM, Cannon CP, Cushman WC, Fleck P, Heller S, Mehta C, Nissen SE, Perez A, Wilson C, Zannad F. EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J 2011;162:620-626.
53. CAROLINA: Cardiovascular outcome study of linagliptin versus glime-piride in patients with type 2 diabetes. http://clinicaltrials.gov/ct2/show/ NCT01243424?term=NCT01243424&rank=1 (accessed 15 November 2011).
54. TECOS. Sitagliptin cardiovascular outcome study (0431-082 AM1) (TECOS). http://clinicaltrials.gov/ct2/show/NCT00790205?term= NCT00790205&rank=1 (accessed 15 November 2011).
55. Bethel MA, Green J, Califf RM, Holman RR. Rationale and design of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). [Abstract]. Diabetes 2009;78(Suppl 1):A639.
56. SAVOR-TIMI. Does saxagliptin reduce the risk of cardiovascular events when used alone or added to Other Diabetes Medications (SAVOR-TIMI53). http://clinicaltrials.gov/ct2/show/NCT01107886 (accessed 15 November 2011).