Rational Pharmacotherapy in Cardiology

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The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

About the Author

A. A. Aleksandrov
Endocrinological Scientific Centre
Russian Federation
Dmitry Ulyanov ul. 11, Moscow, 117036


1. Hambly R.I., Sherman L., Mehta J., Aintablian A. Reappraisal of the role of the diabetic state in coronary artery disease. Chest 1976; 70(2): 251-257.

2. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. TheDiabetes Control and Complications Trial Research Group. N Engl J Med 1993;329(11): 977-986.

3. Nathan D.M., Buse J.B., Davidson M.B. et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statementfrom theAmericanDiabetesAssociation and the EuropeanAssociation forthe Study of Diabetes. Diabetes Care 2008; 31(1): 173-5.

4. Dedov I.I., Shestakova M.V., editors. Algorithms for specialized medical care for patients with diabetes mellitus. 4 th ed. Moscow; 2009. Russian. (Дедов И.И., Шестакова М.В., редакторы. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 4-е изд. М.; 2009).

5. The pharmacological treatment of hyperglycemia in NIDDM. American Diabetes Association. Diabetes Care 1995;18(11):1510-8.

6. Hermann L.S., Schersten B., Bitzen P.O. et al. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.Diabetes Care 1994; 17(10):1100- 1109.

7. Hermann L.S., Schersten B., Melander A. Antihyperglycaemic efficacy, response prediction and doseresponse relations of treatment with metformin and sulphonylurea, alone and in primary combination. Diabet Med 1994;11(10):953-60.

8. DeFronzo R.A., Goodman A.M. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The multicenter metformin study group. N Engl J Med 1995; 333(9): 541-549.

9. Garber A.J., Donovan D.S. Jr, Dandona P. et al. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. J Clin Endocrinol Metab 2003; 88(8): 3598-3604.

10. Nathan D.M. Some answers, more controversy, from UKPDS. United Kingdom Prospective Diabetes Study. Lancet 1998; 352(9131): 832-833.

11. UK Perspective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352(9131): 854-865.

12. Fisman E.Z., Tenenbaum A., Boyko V. et al. Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined gliburid/metformin therapy over a 7.7-year follow-up. Clin Cardiol 2001; 24(2): 151-158.

13. Mannucci E., Monami M., Masotti G., Marchionni N. All-cause mortality in diabetic patients treated with combination of sulfonylureas and biguanides. Diabetes Metab Res Rev 2004; 20(1): 44-47.

14. Olsson J., Lindberg G., Gottsater M. et al. Increased mortality in type 2 diabetic patients using sulfonylurea and metformin in combination: a population-based observational study. Diabetologia 2000; 43(5): 558-560.

15. Bruno G., Merletti F., Boffetta P. et al. Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of type II (non-insulindependent) diabetes mellitus. Diabetologia 1999;42(3): 297-301.

16. Johnson J.A., Simpson S.H., Toth E.L., Majumdar S.R. Redused cardiovascular morbidity and mortality associated with metformin use in subjects with type 2 diabetes. Diabet Med 2005; 22 (4): 497-502.

17. Monami M., Luzzi C., Lamanna C. et al. Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin. Diabetes Metab Res Rev 2006; 22(6): 477-482.

18. Blackburn H. Classification of the electrocardiogram for population studies: Minnesota Code. J Electrocardiol 1969; 2(3): 305-310.

19. Charlson M., Szatrowski T., Peterson J., Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994; 47(11): 1245-1251.

20. Duncker D.J., Van Zon N.S., Altman J.D. et al. Role of K+ATP channels in coronary vasodilation during exercise. Circulation 1993; 88(3): 1245-1253.

21. Cole W.C., McPherson C.D., Sontag D. ATP-regulated K+channels protect the myocardium against ischemia/reperfusion damage. Circ Res1991; 69(3): 571-581.

22. Toombs C.F., McGee D.S., Johnston W.E., Vinten-Johansen J. Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia. Circulation 1992; 86(3):986-994.

23. Pogatsa G., Koltai Z.M., Ballagi-Pordany G. Influence of hypoglycemic sulfonylurea compounds on the incidence of ventricular ectopic beats in non-insulin-dependent diabetic patients treated with digitalis. Curr Ther Res 1993; 53(3): 329-339.

24. Gover G.J., Sleph P.G., Dzwonczyk S. Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interactions with adenosine AI-receptors. Circulation 1992; 86(4):1310-1316.

25. Garratt K.N., Brady P.A., Hassinger N.L. et al. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for myocardial infarction.J Am Coll Cardiol 1999; 33(1): 119-124.

26. Jollis J.G., Simpson R.J., Cascio W.E. et al. Relation between sulfonylurea therapy, complications, and outcome for elderly patients with acute myocardial infarction. Am Heart J 1999; 138(5 Pt 1): S376-S380.

27. KlepzigH., Kober G., Matter C. et al. Sulfonylureas and ischemic preconditioning. A doubl-blind, placebo-controlled evalution of glimepiride and glibenclamide. Eur Heart J 1999; 20(6): 439 -446.

28. Nagashima K., Takahashi A., Ikeda H. et al. Sulfonylurea and non-sulfonylurea hypoglycemic agents: pharmacological properties and tissue selectivity. Diabetes Res Clin Pract 2004;66 Suppl 1: S75-8.

29. Gulliford M., Latinovic R. Mortality in type 2 diabetic subjects prescribed metformin and sulfonylurea drugs in combination: cohord study. Diabetes Metab Res Rev 2004; 20(3):239-245.

30. Ovunc K. Effects of glibenclamide, a K(ATP) channel blocker, on warm-up phenomenon in type 2 diabetic patients with chronic stable angina pectoris. Clin Cardiol 2000; 23(7): 535-539.

31. Wei M., Gibbons L.W., Mitchell T.L. et al. Low Fasting Plasma Glucose Level as a Predictor of Cardiovascular Disease and All-Cause Mortality. Circulation 2000;101(17);2047-2052.

32. Marre M.,HowlettH., Lehert P.,Allavoine T. Improved glycaemic control with metformin–glibenclamide combined tablet therapy (Glucovance) in Type 2 diabetic patients inadequately controlled on metformin. Diabet Med 2002; 19(8): 673-80.

33. Charpentier G., Fleury F., Kabir M. et al. Improved glycaemic control by addition of glimepiride to metformin monotherapy in Type 2 diabetic patients. Diabet Med 2001;18(10): 828-34.

34. Moses R., Slobodniuk R., Boyages S. et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 1999; 22(1):119-24.

35. Adams J.F., Clark L.S., Ireland J.T. et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983; 24(1): 16-18.

36. Mayer E.L., Jacobsen D.W., Robinson K. Homocystein and coronary atherosclerosis. J Am Coll Cardiol 1996; 27(3): 517-527.

37. Nygard O., Nordrehaug L.E., Refsum H. et al. Plasma homocystein levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337(4): 230-236.

38. Innerfield R.J. Metformin-associated mortality in U.S. studies. N Engl J Med 1996; 334: 1611-1613.

39. Fisman E.Z., Tenenbaum A., Benderly M. et al. Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up. Cardiology 1999;91(3):195-202.

40. Goldner M.G., Knatterud G.L., Prout T.E. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. 3. Clinical implications of UGDP results. JAMA 1971; 218(9); 1400-1410.

41. Seltzer H.S. A summary of criticisms of the Findings and conclusions of the university group program (UGDP). Diabetes 1972; 21(9): 976-979.

42. Fisman E.Z., Tenenbaum A. F cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease. Cardiovascular Diabetology 2009; 8:38-51.

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