Patients with type 2 diabetes experience progressive loss of glycaemic control and require intensification of glucose-lowering therapies. Durable glycaemic control has been shown to reduce microvascular and macrovascular complications in patients with type 1 diabetes or type 2 diabetes. The range of available glucose-lowering agents has been expanded with the addition of the thiazolidinediones (TZDs) pioglitazone androsiglitazone and, more recently, dipeptidyl peptidase-4 inhibitors and the glucagon-like peptide-1 analogue exenatide. In clinical trials, the TZDs have provided sustained glycaemic control, both in monotherapy and in combination with metformin and sulphonylureas. Pioglitazone has also been associated with improvements in the long-term cardiovascular morbidity and mortality of patients with type 2 diabetes.Br J Diabetes Vasc Dis 2009;9:53—63
Home P.Contributions of basal and post-prandial hyperglycaemia to micro- and macrovascular complications in people with type 2 diabetes. Curr Med Res Opin2005;21:989-98.
2.
Selvin E., Marinopoulos S., Berkenblit G. et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med2004;141:421-31.
3.
Stettler C., Allemann S., Jüni P. et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J2006;152:27-38.
4.
Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ2000; 321:405-12.
5.
Ohkubo Y., Kishikawa H., Araki E. et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract1995;28:103-17.
6.
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). Lancet1998;352:837-53.
7.
Nathan DM, Cleary PA, Backlund JY et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med2005;353:2643-53.
8.
Fox KM, Gerber RA, Bolinder B. et al. Prevalence of inadequate glycaemic control among patients with type 2 diabetes in the United Kingdom general practice research database: a series of retrospective analyses of data from 1998 through 2002. Clin Ther2006;28:388-95.
9.
Nichols GA, Alexander CM, Girman CJ et al. Treatment escalation and rise in HbA1c following successful initial metformin therapy. Diabetes Care2006 ;29:504-9.
10.
Turner RC, Cull CA, Frighi V. et al. Glycaemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus. Progressive requirement of multiple therapies (UKPDS 49). JAMA1999;281:2005-12.
11.
Brownlee M.Biochemistry and molecular cell biology of diabetic complications. Nature2001;414:813-20.
12.
Esper RJ, Vilarino JO, Machado RA et al. Endothelial dysfunction in normal and abnormal glucose metabolism . Adv Cardiol2008;45:17-43.
13.
Robertson RP , Harmon J., Tran PO et al. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes2003;52:581-7.
14.
Cleary PA, Orchard TJ, Genuth S. et al. The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study. Diabetes2006;55:3556-65.
15.
Writing Team for the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the micro-vascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563-9.
16.
UK Prospective Diabetes Study (UKPDS) Group.Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet1998;352:854-65.
17.
Stratton IM , Holman RRIs the cardioprotective effect of metformin in type 2 diabetes dose dependent [Abstract]?Diabetes2003; 52(suppl 1):A167-8.
18.
Holman RR, Paul SK, Bethel MA et al .10-Year follow-up of intensive glucose control in type 2 Diabetes. UKPDS 80. N Engl J Med2008;359(15):1565-76.
19.
Schellhase KG, Koepsell TD, Weiss NSGlycemic control and the risk of multiple microvascular diabetic complications. Fam Med2005;37:125-30.
20.
ACCORD Study Group.Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol2007;99(12A):21i-33i.
21.
Karalliedde J., Gnudi L.ACCORD and ADVANCE: a tale of two studies on the merits of glycaemic control in type 2 diabetic patients. Nephrol Dial Transplant2008;23:1796-8.
22.
Tan M., Urquhart R., Baksi A. et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care2005;28:544-50.
23.
Mazzone T., Meyer PM, Feinstein SB et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA2006;296:2572-81.
24.
Nissen SE, Nicholls SJ, Wolski K. et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA2008;299:1561-73.
25.
Kahn SE, Heffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med2006;355:2427-43.
26.
Hanefeld M. , Pfützner A., Forst T., Lübben G.Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study. Curr Med Res Opin2006;22:1211-5.
27.
Schernthaner G., Matthews DR, Charbonnel B. et al. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab2004;89:6068-76.
28.
Yamanouchi T., Sakai T., Igarashi K. et al. Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed type 2 diabetes. Diabet Med2005;22:980-5.
29.
Perriello G. , Pampanelli S., Di Pietro C. et al. Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with type 2 diabetes. Diabet Med2006;23:246-52.
30.
Tan M., Johns D., Gonzalez Galvez G. et al. Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, parallel-group trial. Clin Ther2004;26:680-93.
31.
Tan M., Johns D., Strand J. et al. Sustained effects of pioglitazone vs glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with type 2 diabetes. Diabet Med2004;21:859-66.
32.
Hanefeld M. , Patwardhan R., Jones NP et al. A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes . Nutr Metab Cardiovasc Dis2007; 17:13-23.
33.
Charbonnel B., Schernthaner G., Brunetti P. et al. Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes . Diabetologia2005;48:1093-1104.
34.
Derosa G., D'Angelo A., Ragonesi PD et al. Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome. J Clin Pharm Ther2006;31:375-83.
35.
Matthews DR , Charbonnel BH, Hanefeld M. et al. Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized, comparative study . Diabetes Metab Res Rev2005;21:167-74.
36.
Derosa G., Cicero AF, Gaddi A. et al. Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial. Clin Ther2004; 26:744-54.
37.
Hanefeld M. , Charbonnel BH, Brunetti P. et al. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care2004;27:141-7.
38.
Derosa G., Gaddi AV, Ciccarelli L. et al. Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial. J Int Med Res2005;33:284-94.
39.
Rajagopalan R. , Xu Y., Abadesa M. et al. The effect of pioglitazone on glycemic and lipid parameters and adverse events in elderly patients with type 2 diabetes mellitus: a post hoc analysis of four randomized trials. Am J Geriatr Pharmacother2006;4:123-33.
40.
Spanheimer R. , Kupfer S., Perez A. et al. The effects of pioglitazone vs glyburide on glycemic control in patients with type 2 diabetes in a 3-year randomized double-blind trial. Diabetes2006;55(suppl 1): A74-5.
41.
Data on file: Efficacy and safety study of pioglitazone and metformin combination therapy and treating type 2 diabetes. Clinical trial identifier NCT00727857. Takeda Global Research & Development Center, Inc.
42.
Charbonnel B. , Dormandy J., Erdmann E. et al. 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 Care2004;27:1647-53.
43.
Erdmann E., Dormandy J., Wilcox R. et al. PROactive 07: Pioglitazone in the treatment of type 2 diabetes: results of the PROactive study. Vasc Health Clin Risk Management2007;3:355-70.
44.
Chalmers J. , Hunter JE, Robertson SJ et al. Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes . Curr Med Res Opin2007;23:1775-81.
45.
Schweizer A. , Couturier A., Foley JE et al. Comparison between vildagliptin and metformin to sustain reductions in HbA1c over 1 year in drug-naive patients with type 2 diabetes. Diabet Med2007;24:955-61.
46.
Scherbaum WA , Schweizer A., Mari A. et al. Evidence that vildagliptin attenuates deterioration of glycaemic control during 2-year treatment of patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab2008, Mar 18: Epub ahead of print.
47.
Nauck MA, Meininger G., Sheng D. et al. 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 Metab2007;9:194-205.
48.
Rydén L., Standl E., Bartnik M. et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J2007;28:88-136.
49.
Dormandy JA , Charbonnel B., Eckland EJ et al. Secondary prevention of macrovascular events in patients with type 2 diabetes: a randomized trial of pioglitazone. The PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events). Lancet2005;366:1279-89.
50.
Lincoff AM, Wolski K., Nicholls SJ et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a metaanalysis of randomized trials. JAMA2007;298:1180-8.
51.
Home PD, Pocock SJ, Beck-Nielsen H. et al. Rosiglitazone evaluated for cardiovascular outcomes - an interim analysis. N Engl J Med2007;357:28-38.
52.
Nissen SE, Wolski K.Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med2007 ;356:2457-71.
53.
Rosen CJThe rosiglitazone story - lessons from an FDA Advisory Committee Meeting . N Engl J Med2007;357:844-6.
54.
Singh S., Loke YK, Furberg CDLong-term risk of cardiovascular events with rosiglitazone: a metaanalysis . JAMA2007;298:1189-95.
55.
European Medicines Agency Press Office. Doc. Ref. EMEA/42232/2008. Downloaded from http://www.emea.europa.eu/pressoffice/chmp.htm (Accessed 4 October 2008).
