Outcomes and lessons from the PROactive study

Diabetes Research and Clinical Practice

Volumn 98, Issue 2, 2012, Pages 175-186

  Scheen, André J ^a  

^a UNIVERSITY OF LIÈGE   (Belgium)

Author keywords

Cardiovascular outcome; Glucose control; Heart failure; Pioglitazone; PROactive; Thiazolidionedione; Type 2 diabetes mellitus

Indexed keywords

HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SULFONYLUREA;

BODY MASS; CANCER RISK; CARDIOVASCULAR EFFECT; CARDIOVASCULAR RISK; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; CHRONIC KIDNEY DISEASE; CLINICAL EVALUATION; CONGESTIVE HEART FAILURE; COST EFFECTIVENESS ANALYSIS; DISEASE ASSOCIATION; DRUG COST; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; FRACTURE; GLOMERULUS FILTRATION RATE; GLYCEMIC CONTROL; HEART INFARCTION; HEART PROTECTION; HIGH RISK POPULATION; HUMAN; LIPID ANALYSIS; META ANALYSIS (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PATIENT MONITORING; PERIPHERAL OCCLUSIVE ARTERY DISEASE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK REDUCTION; SIDE EFFECT; WEIGHT GAIN;

CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOGLYCEMIC AGENTS; THIAZOLIDINEDIONES;

EID: 84870546935     PISSN: 01688227     EISSN: 18728227     Source Type: Journal    
DOI: 10.1016/j.diabres.2012.09.001     Document Type: Review

References (75)

1. Mazzone T., Chait A., Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 2008, 371:1800-1809.
2. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004, 351:1106-1118.
3. Chan J.Y.C., Ilag L., Tan M.H. Effects of thiazolidinediones on the triad of type 2 diabetes mellitus, insulin resistance and cardiovascular disease. Diabetes Res Clin Pract 2007, 78:S3-S13.
4. Derosa G. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents. Drugs 2010, 70:1945-1961.
5. de Pablos-Velasco P. Pioglitazone: beyond glucose control. Expert Rev Cardiovasc Ther 2010, 8:1057-1067.
6. Barnett A.H. Redefining the role of thiazolidinediones in the management of type 2 diabetes. Vasc Health Risk Manage 2009, 5:141-151.
7. Campbell I.W. Pioglitazone - An oral antidiabetic agent and metabolic syndrome F modulator. Can theory translate into practice?. Br J Diabetes Vasc Dis 2005, 5:209-216.
8. Pfützner A., Schneider C.A., Forst T. Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects. Expert Rev Cardiovasc Ther 2006, 4:445-459.
9. Charbonnel B., Dormandy J., Erdmann E., Massi-Benedetti M., Skene A. The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care 2004, 27:1647-1653. PROactive Study Group.
10. Dormandy J.A., Charbonnel B., Eckland D.J., Erdmann E., Massi-Benedetti M., Moules I.K., et al. 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.
11. Yki-Järvinen H. The PROactive study: some answers, many questions. Lancet 2005, 366:1241-1242.
12. Fonseca V., Jawa A., Asnani S., Commentary: The PROactive study - the glass is half full. J Clin Endocrinol Metab 2006, 91:25-27.
13. Rizza R., Henry R., Kahn R. Commentary on the results and clinical implications of the PROactive study. Diabetes Care 2005, 28:2965-2967.
14. Skyler J.S., PROactive: A sad tale of inappropriate analysis and unjustified interpretation. Clin Diabetes 2006, 24:63-65.
15. Erdmann E., Charbonnel B., Wilcox R. Thiazolidinediones and cardiovascular risk - a question of balance. Curr Cardiol Rev 2009, 5:155-165.
16. Erdmann E., Dormandy J., Wilcox R., Massi-Benedetti M., Charbonnel B. PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study. Vasc Health Risk Manage 2007, 3:355-370.
17. Khanderia U., Pop-Busui R., Eagle K.A. Thiazolidinediones in type 2 diabetes: a cardiology perspective. Ann Pharmacother 2008, 42:1466-1474.
18. Krentz A., Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complications. Diabetes Metab Res Rev 2009, 25:112-126.
19. Ryder R.E.J., Pioglitazone: An agent which reduces stroke, myocardial infarction and death and is also a key component of the modern paradigm for the optimum management of type 2 diabetes. Br J Diabetes Vasc Dis 2011, 11:113-120.
20. Richter B., Bandeira-Echtler E., Bergerhoff K., Clar C., Ebrahim S.H. Pioglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev 2006, CD006060. 10.1002/14651858.CD006060.pub2.
21. Nissen S.E., Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457-2471.
22. Home P.D., Pocock S.J., Beck-Nielsen H., Curtis P.S., Gomis R., Hanefeld M., et al. 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.
23. Loke Y.K., Kwok C.S., Singh S. Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. Br Med J 2011, 342:d1309.
24. Nathan D.M., Buse J.B., Davidson M.B., Ferrannini E., Holman R.R., Sherwin R., et al. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2009, 52:17-30.
25. Pouwels K.B., van Grootheest K. The rosiglitazone decision process at FDA and EMA. What should we learn?. Int J Risk Saf Med 2012, 24:73-80.
26. Betteridge D.J., DeFronzo R.A., Chilton R.J. PROactive: time for a critical appraisal. Eur Heart J 2008, 29:969-983.
27. Dormandy J., Bhattacharya M., Van Troostenburg De Bruyn A.R. Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf 2009, 32:187-202.
28. Kung J., Henry R.R. Thiazolidinedione safety. Expert Opin Drug Saf 2012, 11:565-579.
29. Inzucchi S.E., Bergenstal R.M., Buse J.B., Diamant M., Ferrannini E., Nauck M., et al. Management of hyperglycaemia 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). Diabetologia 2012, 55:1577-1596.
30. Erdmann E., Spanheimer R., Charbonnel B., Investigators P.S. Pioglitazone and the risk of cardiovascular events in patients with Type 2 diabetes receiving concomitant treatment with nitrates, renin-angiotensin system blockers, or insulin: results from the PROactive study (PROactive 20). J Diabetes 2010, 2:212-220.
31. Lincoff A.M., Wolski K., Nicholls S.J., Nissen S.E. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. J Am Med Assoc 2007, 298:1180-1188.
32. Wilcox R., Kupfer S., Erdmann E. Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10). Am Heart J 2008, 155:712-717. PROactive Study investigators.
33. Betteridge D.J. CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with pioglitazone. Fundam Clin Pharmacol 2009, 23:675-679.
34. Erdmann E., Dormandy J.A., Charbonnel B., Massi-Benedetti M., Moules I.K., Skene A.M., et al. The effect of pioglitazone on recurrent myocardial infarction in 2445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) study. J Am Coll Cardiol 2007, 49:1772-1780.
35. Wilcox R., Bousser M.G., Betteridge D.J., Schernthaner G., Pirags V., Kupfer S., et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04). Stroke 2007, 38:865-873.
36. Dormandy J.A., Betteridge D.J., Schernthaner G., Pirags V., Norgren L. Impact of peripheral arterial disease in patients with diabetes - results from PROactive (PROactive 11). Atherosclerosis 2009, 202:272-281. PROactive investigators.
37. Rydén L., Thráinsdóttir I., Swedberg K. Adjudication of serious heart failure in patients from PROactive. Lancet 2007, 369:189-190.
38. Erdmann E., Charbonnel B., Wilcox R.G., Skene A.M., Massi-Benedetti M., Yates J., et al. Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes Care 2007, 30:2773-2778.
39. Pfister R., Cairns R., Erdmann E., Schneider C.A. A clinical risk score for heart failure in patients with type 2 diabetes and macrovascular disease: an analysis of the PROactive study. Int J Cardiol 2011, Pii: S0167-5273(11)00469-4 [Epub ahead of print]. 10.1016/j.ijcard.2011.05.056.
40. Komajda M., McMurray J.J., Beck-Nielsen H., Gomis R., Hanefeld M., Pocock S.J., et al. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Eur Heart J 2010, 31:824-831.
41. Mannucci E., Monami M., Lamanna C., Gensini G.F., Marchionni N. Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials. Diabetes Obes Metab 2008, 10:1221-1238.
42. Macfarlane D.P., Fisher M. Thiazolidinediones in patients with diabetes mellitus and heart failure: implications of emerging data. Am J Cardiovasc Drugs 2006, 6:297-304.
43. Pfister R., Cairns R., Erdmann E., Schneider C.A. Prognostic impact of electrocardiographic signs in patients with type 2 diabetes and cardiovascular disease: results from the PROactive study. Diabet Med 2011, 28:1206-1212.
44. Pfister R., Michels G., Cairns R., Schneider C.A., Erdmann E. Incidence of new onset bundle branch block and atrial fibrillation in patients with type 2 diabetes and macrovascular disease: an analysis of the PROactive study. Int J Cardiol 2011, 153:233-234.
45. Johnson J.A., Bowker S.L. Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia 2011, 54:25-31.
46. Zhu Z., Shen Z., Lu Y., Zhong S., Xu C. Increased risk of bladder cancer with pioglitazone therapy in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2012, [Epub ahead of print]. 10.1016/j.diabres.2012.05.006.
47. Azoulay L., Yin H., Filion K.B., Assayag J., Majdan A., Pollak M.N., et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. Br Med J 2012, 344:e3645.
48. Loke Y.K., Singh S., Furberg C.D. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. Can Med Assoc J 2009, 180:32-39.
49. Bilik D., McEwen L.N., Brown M.B., Pomeroy N.E., Kim C., Asao K., et al. Thiazolidinediones and fractures: evidence from translating research into action for diabetes. J Clin Endocrinol Metab 2010, 95:4560-4565.
50. Doehner W., Erdmann E., Cairns R., Clark A.L., Dormandy J.A., Ferrannini E., et al. Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population. Int J Cardiol 2011, Pii: S0167-5273(11)01768-2 [Epub ahead of print]. 10.1016/j.ijcard.2011.09.039.
51. Sarafidis P.A., Georgianos P.I., Lasaridis A.N. PPAR-gamma agonism for cardiovascular and renal protection. Cardiovasc Ther 2011, 29:377-384.
52. Schneider C.A., Ferrannini E., Defronzo R., Schernthaner G., Yates J., Erdmann E. Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. J Am Soc Nephrol 2008, 19:182-187.
53. Bolignano D., Zoccali C. Glitazones in chronic kidney disease: potential and concerns. Nutr Metab Cardiovasc Dis 2012, 22:167-175.
54. Scheen A.J., Tan M.H., Betteridge D.J., Birkeland K., Schmitz O., Charbonnel B. Long-term glycaemic effects of pioglitazone compared with placebo as add-on treatment to metformin or sulphonylurea monotherapy in PROactive (PROactive 18). Diabet Med 2009, 26:1242-1249.
55. Scheen A.J., Tan M.H., Betteridge D.J., Birkeland K., Schmitz O., Charbonnel B., et al. Long-term glycaemic control with metformin-sulphonylurea-pioglitazone triple therapy in PROactive (PROactive 17). Diabet Med 2009, 26:1033-1039.
56. Charbonnel B., DeFronzo R., Davidson J., Schmitz O., Birkeland K., Pirags V., et al. Pioglitazone use in combination with insulin in the prospective pioglitazone clinical trial in macrovascular events study (PROactive19). J Clin Endocrinol Metab 2010, 95:2163-2171.
57. Scheen A.J. Combined thiazolidinedione-insulin therapy: should we be concerned about safety?. Drug Saf 2004, 27:841-856.
58. Spanheimer R., Betteridge D.J., Tan M.H., Ferrannini E., Charbonnel B. Long-term lipid effects of pioglitazone by baseline anti-hyperglycemia medication therapy and statin use from the PROactive experience (PROactive 14). Am J Cardiol 2009, 104:234-239. PROactive investigators.
59. Ferrannini E., Betteridge D.J., Dormandy J.A., Charbonnel B., Wilcox R.G., Spanheimer R., et al. High-density lipoprotein-cholesterol and not HbA1c was directly related to cardiovascular outcome in PROactive. Diabetes Obes Metab 2011, 13:759-764.
60. Goldberg R.B., Kendall D.M., Deeg M.A., Buse J.B., Zagar A.J., Pinaire J.A., et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005, 28:1547-1554.
61. Betteridge D.J. Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab 2007, 9:640-647.
62. Hanefeld M. The role of pioglitazone in modifying the atherogenic lipoprotein profile. Diabetes Obes Metab 2009, 11:742-756.
63. Derosa G. Pioglitazone is a valid alternative to rosiglitazone. Am J Cardiovasc Drugs 2011, 11:357-362.
64. Tolman K.G. The safety of thiazolidinediones. Expert Opin Drug Saf 2011, 10:419-428.
65. Fisher M. Improving cardiovascular risk - applying evidence-based medicine to glucose-lowering therapy with thiazolidinediones in patients with type 2 diabetes. Int J Clin Pract 2009, 63:1354-1368.
66. Simo R., Rodriguez A., Caveda E. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone. Curr Drug Saf 2010, 5:234-244.
67. Bottomley J., Palmer A.J., Williams R., Dormandy J., Massi-Benedetti M. PROactive 03: pioglitazone, type 2 diabetes and reducing macrovascular events - economic implications?. Br J Diabetes Vasc Dis 2006, 6:63-70.
68. Valentine W.J., Bottomley J.M., Palmer A.J., Brändle M., Foos V., Williams R., et al. PROactive 06: cost-effectiveness of pioglitazone in type 2 diabetes in the UK. Diabet Med 2007, 24:982-1002.
69. Valentine W.J., Tucker D., Palmer A.J., Minshall M.E., Foos V., Silberman C., et al. Long-term cost-effectiveness of pioglitazone versus placebo in addition to existing diabetes treatment: a US analysis based on PROactive. Value Health 2009, 12:1-9.
70. Brändle M., Goodall G., Erny-Albrecht K.M., Erdmann E., Valentine W.F. Cost-effectiveness of pioglitazone in patients with type 2 diabetes and a history of macrovascular disease in a Swiss setting. Swiss Med Wkly 2009, 139:173-184.
71. Bierwirth R., Liebl A., Gschwend M.H. Cost-effectiveness of pioglitazone in patients with type2 diabetes and a history of macrovascular disease in Germany. Med Klin 2010, 5:32-39.
72. Scherbaum W.A., Goodall G., Erny-Albrecht K.M., Massi-Benedetti M., Erdmann E., Valentine W.J. Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective. Cost Eff Resour Alloc 2009, 7:9.
73. Cariou B., Charbonnel B., Staels B. Thiazolidinediones and PPARgamma agonists: time for a reassessment. Trends Endocrinol Metab 2012, 23:205-215.
74. Williams R. Should we be PROactive in prescribing thiazolidinediones?. Pharm Pract 2006, 16:218-221.
75. Singaram V., Pratley R. The PROactive trial (PROspective pioglitAzone Clinical Trial In macroVascular Events): what does it mean for primary care physicians?. Diab Vasc Dis Res 2007, 4:237-240.