Avandamet

Abstract

Type 2 diabetes mellitus is characterised by multiple defects including decreased insulin mediated glucose disposal, higher endogenous glucose production mainly from liver and inadequate pancreatic secretion of insulin. Metformin and thiazolidinediones (TZDs) decrease insulin resistance by different mechanisms of action, and since both have the advantage of decreasing hyperglycaemia without increasing insulin secretion, they make an attractive option for combination. Metformin decreases hepatic glucose production and enhances peripheral glucose uptake while TZDs, by acting on peroxisome proliferator-activated receptor-gamma (PPARγ) receptors increase glucose uptake.

The combination has also been shown to improve glycaemic control, improve insulin sensitivity and improve beta-cell function. The availability of the two drugs in one pill has the potential to improve patientcompliance and decrease costs.

Keywords

combination therapy type 2 diabetes rosiglitazone metformin.

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References

Holman R. The UKPDS: implications for the dyslipidaemic patient. Acta Diabetol 2001;38(suppl 1):S9-S14.

Leslie RD

United Kingdom prospective diabetes study (UKPDS): what now or so what?

Diabetes Metab Res Rev 1999;15(1):65-71.

Nicollerat JA Implications of the United Kingdom Prospective Diabetes Study (UKPDS) results on patient management. Diabetes Educ 2000;26 (suppl):8-10.

Turner RC , Millns H. , Neil HA et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998;316:823-8.

Turner RC , Cull CA , Frighi V. , Holman RR Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281:2005-12.

Inzucchi SE , Maggs DG , Spollett GR et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 1998;338:867-72.

Fonseca V. , Rosenstock J. , Patwardhan R. , Salzman A. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000;283:1695-702.

Jones TA , Sautter M. , Van Gaal LF , Jones NP Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes. Diabetes Obes Metab 2003;5:163-70.

Khan MA , Longley J. Psychosocial Aspects of Diabetes: The Diabetologists' Perspective. Semin Clin Neuropsychiatry 1997;2(1):94-8.

10.

Boden G. , Chen X. , Capulong E. , Mozzoli M. Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes. Diabetes 2001 ;50:810-16.

11.

Steinberg HO , Paradisi G. , Hook G. , Crowder K. , Cronin J. , Baron AD Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 2000;49:1231-8.

12.

Hundal RS , Krssak M. , Dufour S. et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-9.

13.

Gomez-Perez FJ , Fanghanel-Salmon G. , Antonio BJ et al. Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes . Diabetes Metab Res Rev 2002;18:127-34.

14.

Neeser K. , Lubben G. , Siebert U. , Schramm W. Cost effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a german statutory healthcare perspective. Pharmacoeconomics 2004;22: 321-41.

15.

Suzuki M. , Odaka H. , Suzuki N. , Sugiyama Y. , Ikeda H. Effects of combined pioglitazone and metformin on diabetes and obesity in Wistar fatty rats. Clin Exp Pharmacol Physiol 2002;29:269-74.

16.

Meriden T. Progress with thiazolidinediones in the management of type 2 diabetes mellitus . Clin Ther 2004;26:177-90.

17.

Fonseca VA Risk factors for coronary heart disease in diabetes. Ann Intern Med 2000;133:154-6.

18.

Di Cicco RA , Allen A. , Carr A. , Fowles S. , Jorkasky DK , Freed MI Rosiglitazone does not alter the pharmacokinetics of metformin. J Clin Pharmacol 2000;40:1280-5.

19.

Ballary C. , Desai A. Efficacy and safety of a combination of metformin and rosiglitazone in patients with type 2 diabetes mellitus - a postmarketing study. J Indian Med Assoc 2003;101:113-4,123.

20.

Masoudi FA , Wang Y. , Inzucchi SE et al. Metformin and thiazolidinedione use in Medicare patients with heart failure. JAMA 2003;290(1):81-5.

21.

Nesto RW , Bell D. , Bonow RO et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004;27:256-63.

22.

SaitoI. , Folsom AR , Brancati FL , Duncan BB , Chambless LE , McGovern PG Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Ann Intern Med 2000 ;133(2):81-91.