Skip to main content

Advertisement

SpringerLink
Log in

The Effect of Sulphonylureas on the Microvascular and Macrovascular Complications of Diabetes

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Introduction

Type 2 diabetes mellitus is a chronic progressive disease that is characterised by hyperglycaemia and is associated with an increased risk of the development of microvascular complications, such as retinopathy, nephropathy and neuropathy, and cardiovascular disease. With the introduction of newer oral hypoglycaemic agents, there is a need to re-evaluate critically the effectiveness and safety of the older agents, including sulphonylureas, to assess their place in the modern management of type 2 diabetes.

Background

Though no clear benefit of sulphonylureas has been shown with respect to large vessel disease, long term studies have, however, shown benefits in patients with microvascular complications. Studies such as the University Group Diabetes Project raised concerns about the safety profile of sulphonylureas, but large prospective studies such as the UK Prospective Diabetes Study have helped to assuage such concerns to a large degree. Their utility in the peri-infarct period continues to be debatable because of the potential effect on cardiac pre-conditioning.

Conclusion

Though sulphonylureas continue to be a mainstay of treatment in type 2 diabetes, future clinical trials addressing clinically relevant outcomes are indicated with the newer generation of sulphonylureas that are more β cell-specific to address the concerns raised about sulphonylureas and cardiac myocytes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Forouhi NG, Merrick D, Goyder E, Ferguson BA, Abbas J, Lachowycz K, Wild SH. Diabetes prevalence in England, 2001—estimates from an epidemiological model. Diabet Med 2006;23:189–97.

    Article  PubMed  CAS  Google Scholar 

  2. Janbon M, Chaptal J, Vedel A, Schaap J. Accidents hypoglycémiques graves par un sulfamidothiodiazol (le VK 57 ou 2254 RP). Montpellier Med 1942;441:21–2.

    Google Scholar 

  3. Patlak M. New Weapons to Combat an Ancient Disease: Treating Diabetes. FASEB J 2002;16:1853E.

    Article  Google Scholar 

  4. Monami M, Lamanna C, Marchionni N, Mannucci E. Comparison of different drugs as add-on treatments to metformin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2007.

  5. Stratton I, Adler A, Neil A, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405–12.

    Article  PubMed  CAS  Google Scholar 

  6. Brunner E, Shipley M, Witte D, et al. Relation between blood glucose and coronary mortality over 33 years in the Whitehall study. Diabetes Care 2006;29:26–31.

    Article  PubMed  Google Scholar 

  7. Gerstein H. Dysglycaemia: a cardiovascular risk factor. Diabetes Res Clin Pract 1998;40:9–14.

    Article  Google Scholar 

  8. The DECODE study. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. Diabetes Med 2000;26:282–6. (Sep).

    Google Scholar 

  9. 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). Lancet 1998;352:837–53.

    Article  Google Scholar 

  10. Pedersen O, Gæde PH. Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2-study. Metabolism 2003;52:19–23.

    Article  PubMed  CAS  Google Scholar 

  11. Holman R. Long term efficacy of sulphonylureas. Metab Clin Exp 2006;55:S2–5.

    PubMed  CAS  Google Scholar 

  12. Leibowitz G, Cerasi E. Sulphonylurea treatment of NIDDM patients with cardiovascular disease: a mixed blessing? Diabetologia 1996;39:503–14.

    Article  PubMed  CAS  Google Scholar 

  13. Asplund K, Wiholm BE, Lithner F. Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia 1983;24:412–7.

    Article  PubMed  CAS  Google Scholar 

  14. Pagano PJ, Griswold MC, Ravel D, Cohen RA. Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits. Diabetologia 1998;41:9–15.

    Article  PubMed  CAS  Google Scholar 

  15. Okouchi M, Okayama N, Omi H, et al. The antidiabetic agent, gliclazide, reduces high insulin-enhanced neutrophil–transendothelial migration through direct effects on the endothelium. Diabetes Metab Res Rev 2004;20:232–8.

    Article  PubMed  CAS  Google Scholar 

  16. Zaremba J, Losy J. sPECAM-1in serum and CSF of acute ischaemic stroke patients. Acta Neurol Scand 2002;106:292–8.

    Article  PubMed  CAS  Google Scholar 

  17. Soeki T, Tamura Y, Shinohara H, Sakabe K, Onose Y, Fukuda N. Increased sPECAM-1in the early stages of acute coronary syndromes. Int J Cardiol 2003;90:261–8.

    Article  PubMed  Google Scholar 

  18. Katakami N, Yamasaki Y, Hayaishi-Okano R, et al. Metformin or gliclazide, rather than glibenclamide, attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Diabetologia 2004;47:1906–13.

    Article  PubMed  CAS  Google Scholar 

  19. U.K Prospective Diabetes Study (UKPDS) 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 

  20. Meinert CL, Knatterud GL, Prout TE, et al. A study of the effects of hypoglycaemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 1970;19:789–830.

    PubMed  Google Scholar 

  21. Simpson S, Majumdar S, Tsuyuki RT, Eurich D, Johnson J. Dose–response relation between sulphonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ 2006;174:2. (January 17).

    Google Scholar 

  22. Deutsch E, Berger M, Kussmaul WG, Hirschfeld JW Jr, Herrmann HC, Laskey WK. Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolid features. Circulation 1990;82:2044–51.

    PubMed  CAS  Google Scholar 

  23. Kloner RA, Yellon D. Does ischemic preconditioning occur in patients? J Am Coll Cardiol 1994;24:1133–42.

    Article  PubMed  CAS  Google Scholar 

  24. O’Rourke B. Myocardial KATP channels in preconditioning. Circ Res 2000;87:845–55.

    PubMed  CAS  Google Scholar 

  25. Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of KATP channels. Physiol Rev 1998;78:227–45.

    PubMed  CAS  Google Scholar 

  26. Lazdunski M. Ion channel effects of antidiabetic sulfonylureas. Horm Metab Res 1996;28:488–95.

    PubMed  CAS  Google Scholar 

  27. Ashcroft FM. Mechanisms of the glycaemic effects of sulfonylureas. Horm Metab Res 1996;28:456–63.

    Article  PubMed  CAS  Google Scholar 

  28. Riddle M. Editorial: Sulphonylureas differ in effects on ischaemic preconditioning—is it time to retire Glyburide? J Clin Endocrinol Metab 2003;88:528–30.

    Article  PubMed  CAS  Google Scholar 

  29. Lee TM, Chou TF. Impairment of myocardial protection in type 2 diabetic patients. J Clin Endocrinol Metab 2003;88:531–7.

    Article  PubMed  CAS  Google Scholar 

  30. Cacciapuoti F, Spiezia S, Bianchi U, Lama D, D’avino M, Varricchio M. Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus. Am J Cardiol 1991;67:843–47.

    Article  PubMed  CAS  Google Scholar 

  31. Malmberg K, Ryden L, Wedel H, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005;26:650–61.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Development Origins of Health and Disease Division, School of Medicine, University of Southampton, Southampton, SO16 6YD, UK

    Partha Kar & Richard I. G. Holt

  2. IDS Building (MP887), Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Richard I. G. Holt

Authors
  1. Partha Kar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard I. G. Holt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard I. G. Holt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kar, P., Holt, R.I.G. The Effect of Sulphonylureas on the Microvascular and Macrovascular Complications of Diabetes. Cardiovasc Drugs Ther 22, 207–213 (2008). https://doi.org/10.1007/s10557-008-6090-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-008-6090-2

Key words

Search

Navigation