Diabetes clinical trials: Helped or hindered by the current shift in regulatory requirements?

European Heart Journal

Volumn 33, Issue 9, 2012, Pages 1049-1057

  Zannad, Faiez ^a   Stough, Wendy Gattis ^b   Pocock, Stuart J ^c   Sleight, Peter ^d   Cushman, William C ^e   Cleland, John G F ^f   McMurray, John J V ^g   Lonn, Eva ^h   Geller, Nancy L ⁱ   Wedel, Hans ^j   Abadie, Eric ^k   Alonso Garcia, Angeles ^l   Pitt, Bertram ^m  

^a UNIVERSITÉ DE LORRAINE   (France)

^b CAMPBELL UNIVERSITY   (United States)

^c LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

^f CASTLE HILL HOSPITAL   (United Kingdom)

^g UNIVERSITY OF GLASGOW   (United Kingdom)

^h MCMASTER UNIVERSITY   (Canada)

ⁱ NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^j NORDIC SCHOOL OF PUBLIC HEALTH   (Sweden)

^k AFSSAPS   (France)

^l EUROPEAN MEDICINES AGENCY   (United Kingdom)

^m UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

more..

Author keywords

Cardiovascular disease; Clinical trials; Diabetes mellitus

Indexed keywords

ACARBOSE; ALEGLITAZAR; ALOGLIPTIN; CANAGLIFLOZIN; EMPAGLIFLOZIN; EXENDIN 4; GLICLAZIDE; GLIMEPIRIDE; GLIMEPIRIDE PLUS ROSIGLITAZONE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; LINAGLIPTIN; LIRAGLUTIDE; LIXISENATIDE; METFORMIN; PIOGLITAZONE; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA DERIVATIVE;

ALBUMINURIA; AMPUTATION; ATHEROSCLEROSIS; BLINDNESS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CATARACT; CLINICAL TRIAL (TOPIC); DISEASE COURSE; DISEASE MARKER; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; FOOT INJURY; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HEART FAILURE; HEART INFARCTION; HUMAN; HYPOGLYCEMIA; INSULIN RESISTANCE; ISCHEMIC HEART DISEASE; KIDNEY DISEASE; NEUROPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEINURIA; RETINOPATHY; REVIEW; RISK REDUCTION; SYSTEMATIC REVIEW (TOPIC);

ATHEROSCLEROSIS; BIOLOGICAL MARKERS; BLOOD GLUCOSE; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; FEMALE; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIC AGENTS; LEGISLATION, DRUG; MALE; META-ANALYSIS AS TOPIC; MICROCIRCULATION; MYOCARDIAL INFARCTION; RISK FACTORS; STROKE;

EID: 84860637034     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehr437     Document Type: Review

References (62)

1. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381-389.
2. UK Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia 1991;34:877-890.
3. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358:2560-2572.
4. 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. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139.
5. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559.
6. Food and Drug Administration. Guidance for industry diabetes mellitus-evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. http://www fda gov/downloads/drugs/ guidancecomplianceregulatoryinformation/guidances/UCM071627 pdf 2008.
7. 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.
8. Blind E, Dunder K, de Graeff PA, Abadie E. Rosiglitazone: a European regulatory perspective. Diabetologia 2011;54:213-218.
9. Cleland JG, Atkin SL. Thiazolidinediones, deadly sins, surrogates, and elephants. Lancet 2007;370:1103-1104.
10. Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang YH, Stevens GA, Rao M, Ali MK, Riley LM, Robinson CA, Ezzati M. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011;378:31-40.
11. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr, Sowers Jr Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999; 100:1134-1146.
12. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847.
13. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412.
14. Thompson CS. Animal models of diabetes mellitus: relevance to vascular complications. Curr Pharm Des 2008;14:309-324.
15. Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004;141:421-431.
16. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329: 977-986.
17. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-865.
18. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352: 837-853.
19. Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA, Howard BV, Kirkman MS, Kosiborod M, Reaven P, Sherwin RS. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA 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. Circulation 2009;119: 351-357.
20. Chew EY, Ambrosius WT, Davis MD, Danis RP, Gangaputra S, Greven CM, Hubbard L, Esser BA, Lovato JF, Perdue LH, Goff DC Jr, Cushman WC, Ginsberg HN, Elam MB, Genuth S, Gerstein HC, Schubart U, Fine LJ. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233-244.
21. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr, Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian A, O'Connor P, Pop-Busui R, Schubart U, Simmons D, Taylor H, Thomas A, Weiss D, Hramiak I. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010;376:419-430.
22. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589.
23. Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, Grimm RH Jr, Byington RP, Rosenberg YD, Friedewald WT. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011;364:818-828.
24. Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, Dudl RJ, Ismail-Beigi F, Kimel AR, Hoogwerf B, Horowitz KR, Savage PJ, Seaquist ER, Simmons DL, Sivitz WI, Speril-Hillen JM, Sweeney ME. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010;340: b4909.
25. Riddle MC, Ambrosius WT, Brillon DJ, Buse JB, Byington RP, Cohen RM, Goff DC Jr, Malozowski S, Margolis KL, Probstfield JL, Schnall A, Seaquist ER. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care 2010;33: 983-990.
26. Nilsson PM. ACCORD and risk-factor control in type 2 diabetes. N Engl J Med 2010;362:1628-1630.
27. Cefalu WT. Glycemic targets and cardiovascular disease. N Engl J Med 2008;358: 2633-2635.
28. Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med 2008;358:2630-2633.
29. Riddle MC. Counterpoint: intensive glucose control and mortality in ACCORD-still looking for clues. Diabetes Care 2010;33:2722-2724.
30. Lachin JM. Point: intensive glycemic control and mortality in ACCORD-a chance finding? Diabetes Care 2010;33:2719-2721.
31. Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med 2009;151:394-403.
32. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279-1289.
33. 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 mellitus: a meta-analysis of randomised controlled trials. Lancet 2009;373:1765-1772.
34. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassaï B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 2011;343:d4169.
35. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605-613.
36. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009;373:2125-2135.
37. Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, Efendic S, Fisher M, Hamsten A, Herlitz J, Hildebrandt P, MacLeod K, Laakso M, Torp-Pedersen C, Waldenstrom A. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005;26:650-661.
38. Montori VM, Fernandez-Balsells M. Glycemic control in type 2 diabetes: time for an evidence-based about-face? Ann Intern Med 2009;150:803-808.
39. Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL, Zagar T, Poole CD. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet 2010;375:481-489.
40. Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med 1993; 328:1676-1685.
41. Mann JF, Tobe S, Teo KK, Yusuf S. Is therapy of people with chronic kidney disease ONTARGET? Nephrol Dial Transplant 2010;25:42-44.
42. Lind M, Oden A, Fahlen M, Eliasson B. The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects. Diabetologia 2010;53:1093-1098.
43. U.S. National Institutes of Health. http://clinicaltrials.gov 2011; Accessed 3/30/2011.
44. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009;53:S35-S42.
45. Zannad F, Stough WG, Pitt B, Cleland JG, Adams KF, Geller NL, Torp-Pedersen C, Kirwan BA, Follath F. Heart failure as an endpoint in heart failure and non-heart failure cardiovascular clinical trials: the need for a consensus definition. Eur Heart J 2008;29:413-421.
46. Aksnes TA, Kjeldsen SE, Rostrup M, Omvik P, Hua TA, Julius S. Impact of newonset diabetes mellitus on cardiac outcomes in the valsartan antihypertensive long-term use evaluation (VALUE) trial population. Hypertension 2007;50: 467-473.
47. Hartung DM, Touchette DR, Bultemeier NC, Haxby DG. Risk of hospitalization for heart failure associated with thiazolidinedione therapy: a medicaid claimsbased case-control study. Pharmacotherapy 2005;25:1329-1336.
48. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le WM, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 2003;108:2941-2948.
49. Tang WH, Francis GS, Hoogwerf BJ, Young JB. Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. J Am Coll Cardiol 2003;41:1394-1398.
50. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 2007;370:1129-1136.
51. Komajda M, McMurray JJ, Beck-Nielsen H, Gomis R, Hanefeld M, Pocock SJ, Curtis PS, Jones NP, Home PD. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Eur Heart J 2010;31:824-831.
52. Anonymous. Rosiglitazone: seeking a balanced perspective. Lancet 2007;369:1834.
53. Claggett B, Wei LJ. Analytical issues regarding rosiglitazone meta-analysis. Arch Intern Med 2011;171:179-180.
54. Diamond GA, Bax L, Kaul S. Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med 2007;147:578-581.
55. Krall RL. Cardiovascular safety of rosiglitazone. Lancet 2007;369:1995-1996.
56. Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005;294: 2581-2586.
57. Woodcock J, Sharfstein JM, Hamburg M. Regulatory action on rosiglitazone by the U.S. Food and Drug Administration. N Engl J Med 2010;363:1489-1491.
58. Goldfine AB. Assessing the cardiovascular safety of diabetes therapies. N Engl J Med 2008;359:1092-1095.
59. Drucker DJ, Goldfine AB. Cardiovascular safety and diabetes drug development. Lancet 2011;377:977-979.
60. Preiss D, Sattar N, McMurray JJ. A systematic review of event rates in clinical trials in diabetes mellitus: the importance of quantifying baseline cardiovascular disease history and proteinuria and implications for clinical trial design. Am Heart J 2011; 161:210-219.
61. Cleland JG, Witte K, Steel S. Calcium supplements in people with osteoporosis. BMJ 2010;341:c3856.
62. Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J 2008;155:26-32, 32.