Skip to main content

Advertisement

SpringerLink
Log in

Antihypertensive drugs and incidence of type 2 diabetes: Evidence and implications for clinical practice

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

The major antihypertensive drug classes appear to exert differing effects on glycemic control and diabetes incidence. Thiazide diuretic and β-blockers are potentially diabetogenic, whereas calcium channel blockers appear neutral. Inhibitors of the renin-angiotensin system are associated with improvements in glycemic control and may lower diabetes incidence, but it is not clear if this represents a truly preventive effect. Also, it should be noted that previous studies have reported inconsistent results, and the data to date are not definitive. We suggest that inhibitors of the renin-angiotensin system be used as first-line agents in uncomplicated hypertensive patients who are at high risk for developing type 2 diabetes. Thiazides and β-blockers should not be avoided in patients with compelling indications for these drugs. Many hypertensive patients (particularly those who are obese or have prediabetes) require several agents to achieve target blood pressure levels. Therefore, the choice of initial agent is far less important than ensuring that target blood pressure goals are reached.

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 and Recommended Reading

  1. Centers for Disease Control and Prevention: National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2000. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2002.

    Google Scholar 

  2. Edelstein SL, Knowler WC, Bain RP, et al.: Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies. Diabetes 1997, 46:701–710.

    Article  PubMed  CAS  Google Scholar 

  3. Wild S, Roglic G, Green A, et al.: Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27:1047–1053.

    Article  PubMed  Google Scholar 

  4. Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996, 334:374–381.

    Article  PubMed  CAS  Google Scholar 

  5. Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002, 287:356–359.

    Article  PubMed  Google Scholar 

  6. Padwal R, Laupacis A: Antihypertensive therapy and incidence of type 2 diabetes: a systematic review. Diabetes Care 2004, 27:247–255. A systematic review summarizing previous studies.

    Article  PubMed  Google Scholar 

  7. Jandeleit-Dahm KA, Tikellis C, Reid CM, et al.: Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens 2005, 23:463–473.

    Article  PubMed  CAS  Google Scholar 

  8. Janke J, Engeli S, Gorzelniak K, et al.: Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes 2002, 51:1699–1707.

    Article  PubMed  CAS  Google Scholar 

  9. Sharma AM, Janke J, Gorzelniak K, et al.: Angiotensin blockade prevents type 2 diabetes by formation of fat cells. Hypertension 2002, 40:609–611.

    Article  PubMed  CAS  Google Scholar 

  10. Kon V, Jabs K: Angiotensin in atherosclerosis. Curr Opin Nephrol Hypertens 2004, 13:291–297.

    Article  PubMed  CAS  Google Scholar 

  11. Benson SC, Pershadsingh HA, Ho CI, et al.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension 2004, 43:993–1002.

    Article  PubMed  CAS  Google Scholar 

  12. Houston MC: The effects of antihypertensive drugs on glucose intolerance in hypertensive nondiabetics and diabetics. Am Heart J 1988, 115:640–656.

    Article  PubMed  CAS  Google Scholar 

  13. Trost BN, Weidmann P: Effects of calcium antagonists on glucose homeostasis and serum lipids in non-diabetic and diabetic subjects: a review. J Hypertens Suppl 1987, 5:S81-S104.

    Article  PubMed  CAS  Google Scholar 

  14. Pitre M, Gaudreault N, Santure M, et al.: Isradipine and insulin sensitivity in hypertensive rats. Am J Physiol 1999, 276:E1038-E1048.

    PubMed  CAS  Google Scholar 

  15. Wicklmayr M, Rett K, Dietze G, et al.: Effects of beta-blocking agents on insulin secretion and glucose disposal. Horm Metab Res Suppl 1990, 22:29–33.

    PubMed  CAS  Google Scholar 

  16. Cerasi E, Luft R, Efendic S: Effect of adrenergic blocking agents on insulin response to glucose infusion in man. Acta Endocrinol (Copenh) 1972, 69:335–346.

    CAS  Google Scholar 

  17. Pollare T, Lithell H, Selinus I, et al.: Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients. BMJ 1989, 298:1152–1157.

    PubMed  CAS  Google Scholar 

  18. Jacob S, Rett K, Henriksen EJ: Antihypertensive therapy and insulin sensitivity: Do we have to redefine the role of beta-blocking agents? Am J Hypertens 1998, 11:1258–1265.

    Article  PubMed  CAS  Google Scholar 

  19. Pollare T, Lithell H, Berne C: A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989, 321:868–873.

    Article  PubMed  CAS  Google Scholar 

  20. Fajans SS, Floyd JC Jr, Knopf RF, et al.: Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man. J Clin Invest 1966, 45:481–492.

    Article  PubMed  CAS  Google Scholar 

  21. Lake CR, Ziegler MG, Coleman MD, et al.: Hydrochlorothiazide-induced sympathetic hyperactivity in hypertensive patients. Clin Pharmacol Ther 1979, 26:428–432.

    PubMed  CAS  Google Scholar 

  22. Harper R, Ennis CN, Heaney AP, et al.: A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM. Diabetologia 1995, 38:853–859.

    Article  PubMed  CAS  Google Scholar 

  23. Harper R, Ennis CN, Sheridan B, et al.: Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension. BMJ 1994, 309:226–230.

    PubMed  CAS  Google Scholar 

  24. Rowe JW, Tobin JD, Rosa RM, et al.: Effect of experimental potassium deficiency on glucose and insulin metabolism. Metabolism 1980, 29:498–502.

    Article  PubMed  CAS  Google Scholar 

  25. Gorden P, Sherman BM, Simopoulos AP: Glucose intolerance with hypokalemia: an increased proportion of circulating proinsulin-like component. J Clin Endocrinol Metab 1972, 34:235–240.

    Article  PubMed  CAS  Google Scholar 

  26. Helderman JH, Elahi D, Andersen DK, et al.: Prevention of the glucose intolerance of thiazide diuretics by maintenance of body potassium. Diabetes 1983, 32:106–111.

    Article  PubMed  CAS  Google Scholar 

  27. Carlsen JE, Kober L, Torp-Pedersen C, et al.: Relation between dose of bendrofluazide, antihypertensive effect, and adverse biochemical effects. BMJ 1990, 300:975–978.

    Article  PubMed  CAS  Google Scholar 

  28. Padwal R, Majumdar SR, Johnson JA, et al.: A systematic review of drug therapy to delay or prevent type 2 diabetes. Diabetes Care 2005, 28:736–744. This is the most recent systematic review examining the effects of drugs on diabetes incidence.

    Article  PubMed  CAS  Google Scholar 

  29. Gress TW, Nieto FJ, Shahar E, et al.: Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med 2000, 342:905–912. An observational study comparing β-blockers, thiazides, ACE inhibitors, and calcium channel blockers.

    Article  PubMed  CAS  Google Scholar 

  30. Padwal R, Mamdani M, Alter DA, et al.: Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort. Diabetes Care 2004, 27:2458–2463.

    Article  PubMed  Google Scholar 

  31. Verdecchia P, Reboldi G, Angeli F, et al.: Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension 2004, 43:963–969.

    Article  PubMed  CAS  Google Scholar 

  32. Savage PJ, Pressel SL, Curb JD, et al.: Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. Arch Intern Med 1998, 158:741–751.

    Article  PubMed  CAS  Google Scholar 

  33. Fletcher A, Amery A, Birkenhager W, et al.: Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly. J Hypertens 1991, 9:225–230.

    Article  PubMed  CAS  Google Scholar 

  34. Kostis JB, Wilson AC, Freudenberger RS, et al.: Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol 2005, 95:29–35.

    Article  PubMed  CAS  Google Scholar 

  35. Yusuf S, Gerstein H, Hoogwerf B, et al.: Ramipril and the development of diabetes. JAMA 2001, 286:1882–1885.

    Article  PubMed  CAS  Google Scholar 

  36. Vermes E, Ducharme A, Bourassa MG, et al.: Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD). Circulation 2003, 107:1291–1296.

    Article  PubMed  CAS  Google Scholar 

  37. Braunwald E, Domanski MJ, Fowler SE, et al.: Angiotensinconverting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004, 351:2058–2068.

    Article  PubMed  CAS  Google Scholar 

  38. Pfeffer MA, Swedberg K, Granger CB, et al.: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003, 362:759–766.

    Article  PubMed  CAS  Google Scholar 

  39. Lithell H, Hansson L, Skoog I, et al.: The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003, 21:875–886.

    Article  PubMed  CAS  Google Scholar 

  40. UK Prospective Diabetes Study Group: UK prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 1995, 44:1249–1258.

    Article  Google Scholar 

  41. Staessen JA, Wang JG, Thijs L: Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001, 358:1305–1315.

    Article  PubMed  CAS  Google Scholar 

  42. Blood Pressure Lowering Treatment Trialists’ Collaboration: Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectivelydesigned overviews of randomised trials. Lancet 2003, 362:1527–1535.

    Article  CAS  Google Scholar 

  43. Freemantle N, Cleland J, Young P, et al.: Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999, 318:1730–1737.

    PubMed  CAS  Google Scholar 

  44. Heidenreich PA, Lee TT, Massie BM: Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 1997, 30:27–34.

    Article  PubMed  CAS  Google Scholar 

  45. Khan NA, McAlister FA, Campbell NR, et al.: The 2004 Canadian recommendations for the management of hypertension: Part II—Therapy. Can J Cardiol 2004, 20:41–54.

    PubMed  Google Scholar 

  46. Chobanian AV, Bakris GL, Black HR, et al.: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. Hypertension 2003, 42:1206–1252.

    Article  PubMed  CAS  Google Scholar 

  47. Fox KM: Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003, 362:782–788.

    Article  PubMed  CAS  Google Scholar 

  48. Wolf-Maier K, Cooper RS, Kramer H, et al.: Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension 2004, 43:10–17.

    Article  PubMed  CAS  Google Scholar 

  49. Appel LJ: The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA 2002, 288:3039–3042.

    Article  PubMed  Google Scholar 

  50. Gerstein HC, Yusuf S, Holman R, et al.: Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 2004, 47:1519–1527.

    Article  PubMed  CAS  Google Scholar 

  51. Navigator press release. The NAVIGATOR study [article online]. Available from http://www.bioportfolio.com/news/ novartis_2.htm. Accessed May 2005.

  52. Yusuf S: From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis. Am J Cardiol 2002, 89(Suppl):18A-26A.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of General Internal Medicine, University of Alberta Hospital, 2E3.22 Walter C. Mackenzie Health Sciences Center, T6G 2B7, Edmonton, AB, Canada

    Samuel Asfaha MD, PhD & Raj Padwal MD, MSc

Authors
  1. Samuel Asfaha MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raj Padwal MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asfaha, S., Padwal, R. Antihypertensive drugs and incidence of type 2 diabetes: Evidence and implications for clinical practice. Current Science Inc 7, 314–322 (2005). https://doi.org/10.1007/s11906-005-0063-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-005-0063-7

Keywords

Search

Navigation