Skip to main content
Log in

Antidiabetic Drugs Present and Future

Will Improving Insulin Resistance Benefit Cardiovascular Risk in Type 2 Diabetes Mellitus?

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Results from the United Kingdom Prospective Diabetes Study showed that intensive treatment of type 2 (non-insulin—dependent) diabetes mellitus, with sulphonylureas or insulin, significantly reduced microvascular complications but did not have a significant effect on macrovascular complications after 10 years. Insulin resistance plays a key role in type 2 diabetes mellitus and is linked to a cluster of cardiovascular risk factors. Optimal treatment for type 2 diabetes mellitus should aim to improve insulin resistance and the associated cardiovascular risk factors in addition to achieving glycaemic control. Treatment with sulphonylureas or exogenous insulin improves glycaemic control by increasing insulin supplies rather than reducing insulin resistance. Metformin and the recently intraduced thiazolidinediones have beneficial effects on reducing insulin resistance as well as providing glycaemic control. There is evidence that, like metformin, thiazolidinediones also improve cardiovascular risk factors such as dyslipidaemia and fibrinolysis. Whether these differences will translate into clinical benefit remains to be seen. The thiazolidinediones rosiglitazone and pioglitazone have been available in the US since 1999 (with pioglitazone also being available in Japan). Both products are now available to physicians in Europe.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I

Similar content being viewed by others

References

  1. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus [committee Report]. Diabetes Care 1999; 22: S5–19

    Google Scholar 

  2. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86

    Article  Google Scholar 

  3. Reichard P, Nilsson B–Y, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993; 329: 304–9

    Article  PubMed  CAS  Google Scholar 

  4. 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 Pract 1995; 28: 103–17

    Article  PubMed  CAS  Google Scholar 

  5. UK Prospective Diabetes Study 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). Lancet 1998; 352: 837–53

    Article  Google Scholar 

  6. Turner R, Cull C, Holman R. United Kingdom Prospective diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med 1996; 124: 136–45

    PubMed  CAS  Google Scholar 

  7. Stout RW. Insulin and atheroma. Diabetes Care 1990; 13: 631–54

    Article  PubMed  CAS  Google Scholar 

  8. Sobel BE. Insulin resistance and thrombosis: a cardiologist’s view. Am J Cardiol 1999; 84: 37J–41

    Article  PubMed  CAS  Google Scholar 

  9. Després J–P, Lamarche B, Mauriège P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952–7

    Article  PubMed  Google Scholar 

  10. Perry IJ, Wannamethee SG, Whincup PH, et al. Serum insulin and incident coronary heart disease in middle-aged British men. Am J Epidemiol 1996; 144: 224–34

    Article  PubMed  CAS  Google Scholar 

  11. Waldhäusl W. Role of sulphonylureas in non-insulin-dependent diabetes mellitus: part 1 — ‘The pros’. Horm Metab Res 1996; 28: 517–21

    Article  PubMed  Google Scholar 

  12. Kolterman OG. Glyburide in non-insulin-dependent diabetes: an update. Clin Ther 1992; 14: 196–213

    PubMed  CAS  Google Scholar 

  13. Langtry HD, Balfour JA. Glimepiride: a review of its use in the management of type 2 diabetes mellitus. Drugs 1998; 55: 563–84

    Article  PubMed  CAS  Google Scholar 

  14. Wolffenbuttel BHR, van Haeften TW. Prevention of complications in non-insulin-dependent diabetes mellitus (NIDDM). Drugs 1995; 50: 263–88

    Article  PubMed  CAS  Google Scholar 

  15. Colwell JA. Pathophysiology of vascular disease in diabetes: effects of gliclazide. Am J Med 1991; 90 Suppl. 6A: 50S–4

    Article  PubMed  CAS  Google Scholar 

  16. UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65

    Article  Google Scholar 

  17. Krentz AJ, Ferner RE, Bailey CJ. Comparative tolerability profiles of oral antidiabetic agents. Drug Saf 1994; 11: 223–41

    Article  PubMed  CAS  Google Scholar 

  18. O’Keefe JH, Miles JM, Harris WH, et al. Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clin Proc 1999; 74: 171–80

    Article  PubMed  Google Scholar 

  19. University Group Diabetes Program. A study of the effects of hypoglycaemic agents on vascular complications in patients with adult-onset diabetes: VI Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes 1976; 25: 1129–53

    Google Scholar 

  20. Smits P, Bijlstra PJ, Russel FGM, et al. Cardiovascular effects of sulphonylurea derivatives. Diabetes Res Clin Pract 1996; 31: S55–9

    Article  PubMed  CAS  Google Scholar 

  21. Berger M. Jörgens B, Mühlhauser. Rationale for the use of insulin therapy alone as the pharmacological treatment of type 2 diabetes. Diabetes Care 1999; 22: C71–5

    Article  PubMed  Google Scholar 

  22. Végh A, Papp JG. Haemodynamic and other effects of sulphonylurea drugs on the heart. Diabetes Res Clin Pract 1996; 31: S43–53

    Article  PubMed  Google Scholar 

  23. De Fronzo RA, Barzilai N, Simonson DC. Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metab 1991; 73: 1294–301

    Article  Google Scholar 

  24. Schwartz SL, Goldberg RB, Strange P. Repaglinide in type 2 diabetes: a randomized, double blind, placebo-controlled, dose-response study: Repaglinide Study Group [abstract]. Diabetes 1998; 47 Suppl. 1: A98

    Article  Google Scholar 

  25. 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: 119–24

    Article  PubMed  CAS  Google Scholar 

  26. Klepser TB, Kelly MW. Metformin hydrochloride: an antihyperglycemic agent. Am J Health Syst Pharm 1997; 54: 893–903

    PubMed  CAS  Google Scholar 

  27. Sirtori CR, Pasik C. Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. Pharm Res 1994; 30: 187–224

    Article  CAS  Google Scholar 

  28. Dunn CJ, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995; 49: 721–49

    Article  PubMed  CAS  Google Scholar 

  29. Bailey CJ. Biguanides and NIDDM. Diabetes Care 1992; 15: 755–72

    Article  PubMed  CAS  Google Scholar 

  30. Hollenbeck CB, Johnston P, Varasteh BB, et al. Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non-insulin dependent diabetes by glucose tolerance test criteria. Diabetes Metab 1991; 17: 483–9

    CAS  Google Scholar 

  31. Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care 1993; 16: 621–9

    Article  PubMed  CAS  Google Scholar 

  32. Wu M-S, Johnston P, Sheu WH-H, et al. Effect of metformin on carbohydrate metabolism in NIDDM patients. Diabetes Care 1990; 13: 1–8

    Article  PubMed  CAS  Google Scholar 

  33. Rains SGH, Wilson GA, Richmond W, et al. The effect of glibenclamide and metformin on serum lipoproteins in type 2 diabetes. Diabet Med 1988; 5: 653–8

    Article  PubMed  CAS  Google Scholar 

  34. Chan NN, Brain HPS, Feher MD. Metformin-associated lactic acidosis: a rare of very rare clinical entity? Diabet Med 1999; 16: 273–81

    CAS  Google Scholar 

  35. Plosker GL, Faulds D. Troglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs 1999; 57: 409–38

    Article  PubMed  CAS  Google Scholar 

  36. Day C. Thiazolidinediones: a new class of antidiabetic drugs. Diabet Med 1999; 16: 1–14

    Article  Google Scholar 

  37. Medical Economics Company Inc. Physicians Desk Reference [online]. Available from: http://www.pdr.net [Accessed 2000 Sep 20]

  38. Gomis R, Jones NP, Vallance SE, et al. Low-dose rosiglitazone (RSG) provides additional glycemic control when combined with sulfonylureas in type 2 diabetes (T2D) [plus poster]. Diabetes 1999; 48 Suppl. 1: 63

    Google Scholar 

  39. Fonseca V, Biswas N, Salzman A, et al. Once-daily rosiglitazone in combination with metformin effectively reduces hyperglycemia in patients with type 2 diabetes [plus poster]. Diabetes 1999; 48 Suppl. 1: 100

    Google Scholar 

  40. Raskin P, Dole JF, Rappaport EB, et al. Rosiglitazone improves glycemic control in poorly-controlled, insulin-treated type 2 diabetes [plus poster]. Diabetes 1999; 48 Suppl. 1: 94

    Article  Google Scholar 

  41. Schneider R, Lessem J, Lekich R, et al. Pioglitazone is effective in the treatment of patients with type 2 diabetes. Diabetes 1999; 48 Suppl. 1: 109

    Google Scholar 

  42. Kumar S, Boulton AJM, Beck-Nielsen H, et al. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Diabetologia 1996; 39: 701–9

    Article  PubMed  CAS  Google Scholar 

  43. Goldstein B, Salzman A. Rosiglitazone is effective in poorly controlled type 2 diabetes patients. Diabetologia 1999; 42 Suppl. 1: 229

    Google Scholar 

  44. Salzman A. Rosiglitazone is not associated with hepatoxicity. Diabetologia 1999; 42: A3

    Article  Google Scholar 

  45. Food and Drug Administration (FDA). Rezulin to be withdrawn from the market [press release]. Washington (DC): FDA, 21 March 2000

    Google Scholar 

  46. Parfitt K, editor. Martindale: the complete drug reference. 32nd ed. London: Pharmaceutical Press, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Campbell, I.W. Antidiabetic Drugs Present and Future. Drugs 60, 1017–1028 (2000). https://doi.org/10.2165/00003495-200060050-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200060050-00004

Keywords

Navigation