The Glycemic Effects of Antihypertensive Medications

  • Joshua I. Barzilay
  • Barry R. Davis
  • Paul K. Whelton
Antihypertensive Agents: Mechanisms of Drug Action (M Ernst, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Antihypertensive Agents: Mechanisms of Drug Action


Older antihypertensive medications are believed to be associated with metabolic disturbances, especially raised glucose levels. Owing to this, many physicians shun their use. Newer antihypertensive medications are metabolically neutral or metabolically favorable; therefore, they are looked upon favorably and are chosen as primary medications for the treatment of hypertension. Here we review the literature on the glucose effects of older and newer antihypertensive medications. We also consider what, if any, impact these metabolic effects have on cardiovascular disease outcomes. We show that the diabetogenic effects of thiazide diuretics and beta blockers are small relative to the glucose effects of angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers, and that over time, the glucose differences between older and newer medications diminish. Importantly, we show that the diabetogenic effects of older antihypertensive medications do not translate into increased cardiovascular disease risk.


Diabetes Hypertension Risk Chlorthalidone Lisinopril Amlodipine Beta blocker ALLHAT Cardiovascular disease Side effect 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:f2610.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Muscogiuri G, Chavez AO, Gastaldelli A, Perego L, Tripathy D, Saad MJ, et al. The crosstalk between insulin and renin-angiotensin-aldosterone signaling systems and its effect on glucose metabolism and diabetes prevention. Curr Vasc Pharmacol. 2008;6:301–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab. 2004;30:498–505.PubMedCrossRefGoogle Scholar
  4. 4.
    Shafi T, Appel LJ, Miller 3rd ER, Klag MJ, Parekh RS. Changes in serum potassium mediate thiazide-induced diabetes. Hypertension. 2008;52:1022–9.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Aksnes TA, Kjeldsen SE, Mancia G. The effect of antihypertensive agents on new-onset diabetes mellitus: time to amend the guidelines? Am J Cardiovasc Drugs. 2006;6:139–47.PubMedCrossRefGoogle Scholar
  6. 6.
    Noto H, Goto A, Tsujimoto T, Noda M. Effect of calcium channel blockers on incidence of diabetes: a meta-analysis. Diabetes Metab Syndr Obes. 2013;6:257–61.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.•
    Lleva RR, Inzucchi SE. Glucose, blood pressure, and cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2012;5:145–7. An informative review of the effects of anti-hypertensive medications on glucose metabolism.PubMedCrossRefGoogle Scholar
  8. 8.
    Yusuf S, Gerstein H, Hoogwerf B, et al. HOPE Study Investigators. Ramipril and the development of diabetes. JAMA. 2001;286:1882–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Holman RR, Haffner SM, McMurray JJ, et al. NAVIGATOR Study Group. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:1463–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Bosch J, Yusuf S, Gerstein HC, et al. DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355:1551–62.PubMedCrossRefGoogle Scholar
  11. 11.
    Barzilay JI, Gao P, Rydén L, Schumacher H, Probstfield J, Commerford P, et al. Effects of telmisartan on glucose levels in people at high risk for cardiovascular disease but free from diabetes: The TRANSCEND Study. Diabetes Care. 2011;34:1902–7.PubMedCrossRefGoogle Scholar
  12. 12.
    European Society of Hypertension-European Society of Cardiology. 2013 Guidelines for the management of arterial hypertension. Available at:
  13. 13.
    Hypertension NICE. Management of Hypertension in Adults with Primary Care – Partial Update. London: National Institute of Health and Clinical Excellence; 2006.Google Scholar
  14. 14.•
    Padwal R, Laupacis A. Antihypertensive therapy and incidence of type 2 diabetes. A systemic review. Diabetes Care. 2004;27:247–55. A review of anti-hypertension studies and the effects of medications on glycemia.PubMedCrossRefGoogle Scholar
  15. 15.•
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369(9557):201–7. A review of anti-hypertension studies and the effects of medications on glycemia.PubMedCrossRefGoogle Scholar
  16. 16.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981–97.CrossRefGoogle Scholar
  17. 17.
    Barzilay JI, Davis BR, Cutler J, et al. Fasting glucose levels and incident diabetes mellitus in older non-diabetic adults randomized to three different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2006;166:2191–201.PubMedCrossRefGoogle Scholar
  18. 18.
    Kostis JB, Wilson AC, Freudenberger RS, Cosgrove NM, Pressel SL, Davis BR. 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.PubMedCrossRefGoogle Scholar
  19. 19.
    Samuelsson O, Pennert K, Andersson O, et al. Diabetes mellitus and raised serum triglyceride concentration in treated hypertension: are they of prognostic importance? observational study. BMJ. 1996;313:660–3.PubMedCrossRefGoogle Scholar
  20. 20.
    The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406–12.CrossRefGoogle Scholar
  21. 21.
    Rowe JW, Tobin JD, Rosa RM, Andres R. Effect of experimental potassium deficiency on glucose and insulin metabolism. Metabolism. 1980;29:498–502.PubMedCrossRefGoogle Scholar
  22. 22.•
    Barzilay JI, Davis BR, Pressel SL, Cutler JA, Einhorn PT, Black HR, et al. ALLHAT Collaborative Research Group. Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study. Circ Cardiovasc Qual Outcome. 2012;5:153–62. A 10-year follow-up of ALLHAT and the effects of incident diabetes associated with the three antihypertensive medications used during the trial on CVD outcomes.CrossRefGoogle Scholar
  23. 23.
    Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.PubMedCrossRefGoogle Scholar
  24. 24.
    Kveiborg B, Hermann TS, Major-Pedersen A, Christiansen B, Rask-Madsen C, Raunsø J, et al. Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes—a randomized study. Cardiovasc Diabetol. 2010;9:21.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998; 317: 713–720.Google Scholar
  26. 26.
    A randomized trial of propranolol in patients with acute myocardial infarction. II. Morbidity results. JAMA 1983; 250: 2814–2819.Google Scholar
  27. 27.
    Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998;339:489–97.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen J, Marciniak TA, Radford MJ, Wang Y, Krumholz HM. Beta-blocker therapy for secondary prevention of myocardial infarction in elderly diabetic patients. Results from the National Cooperative Cardiovascular Project. J Am Coll Cardiol. 1999;34:1388–94.PubMedCrossRefGoogle Scholar
  29. 29.
    Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med. 2000;342:905–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Samuelsson O, Hedner T, Berglund G, Persson B, Andersson OK, Wilhelmsen L. Diabetes mellitus in treated hypertension: incidence, predictive factors and the impact of non-selective beta-blockers and thiazide diuretics during 15 years treatment of middle-aged hypertensive men in the Primary Prevention Trial Goteborg, Sweden. J Hum Hypertens. 1994;8:257–63.PubMedGoogle Scholar
  31. 31.
    Padwal R, Mamdani M, Alter DA, Hux JE, Rothwell DM, Tu K, et al. Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort. Diabetes Care. 2004;27:2458–63.PubMedCrossRefGoogle Scholar
  32. 32.
    Propranolol or hydrochlorothiazide alone for the initial treatment of hypertension. IV. Effect on plasma glucose and glucose tolerance. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Hypertension 1985; 7(6 Pt 1):1008–1016.Google Scholar
  33. 33.
    Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Report of Medical Research Council Working Party on Mild to Moderate Hypertension. Lancet 1981; 2(8246): 539–543.Google Scholar
  34. 34.
    Helgeland A, Leren P, Foss OP, Hjermann I, Holme I, Lund-Larsen PG. Serum glucose levels during long-term observation of treated and untreated men with mild hypertension. The Oslo study. Am J Med. 1984;76:802–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Savage PJ, Pressel SL, Curb JD, Schron EB, Applegate WB, Black HR, 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;158:741–51.PubMedCrossRefGoogle Scholar
  36. 36.
    Wassertheil-Smoller S, Psaty B, Greenland P, Oberman A, Kotchen T, Mouton C, et al. Association between cardiovascular outcomes and antihypertensive drug treatment in older women. JAMA. 2004;292:2849–59.PubMedCrossRefGoogle Scholar
  37. 37.
    Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks. Curr Opin Cardiol. 2013;28:554–60.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Joshua I. Barzilay
    • 1
    • 2
  • Barry R. Davis
    • 3
  • Paul K. Whelton
    • 4
  1. 1.Kaiser Permanente of GeorgiaAtlantaUSA
  2. 2.Division of EndocrinologyEmory University School of MedicineAtlantaUSA
  3. 3.Division of Biostatistics, School of Public HealthUniversity of Texas Medical CenterHoustonUSA
  4. 4.School of Public Health and Tropical MedicineTulane UniversityNew OrleansUSA

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