Advertisement

A Meta-Analysis of 94,492 Patients With Hypertension Treated With Beta Blockers to Determine the Risk of New-Onset Diabetes Mellitus

      Beta blockers used for the treatment of hypertension may be associated with increased risk for new-onset diabetes mellitus (DM). A search of Medline, PubMed, and EMBASE was conducted for randomized controlled trials of patients taking β blockers as first-line therapy for hypertension with data on new-onset DM and follow-up for ≥1 year. Twelve studies evaluating 94,492 patients fulfilled the inclusion criteria. Beta-blocker therapy resulted in a 22% increased risk for new-onset DM (relative risk 1.22, 95% confidence interval [CI] 1.12 to 1.33) compared with nondiuretic antihypertensive agents. A higher baseline fasting glucose level (odds ratio [OR] 1.01, 95% CI 1.00 to 1.02, p = 0.004) and greater systolic (OR 1.05, 95% CI 1.05 to 1.08, p = 0.001) and diastolic (OR 1.06, 95% CI 1.01 to 1.10, p = 0.011) blood pressure differences between the 2 treatment modalities were significant univariate predictors of new-onset DM. Multivariate meta-regression analysis showed that a higher baseline body mass index (OR 1.17, 95% CI 1.01 to 1.33, p = 0.034) was a significant predictor of new-onset DM. The risk for DM was greater with atenolol, in the elderly, and in studies in which β blockers were less efficacious antihypertensive agents and increased exponentially with increased duration on β blockers. For the secondary end points, β blockers resulted in a 15% increased risk for stroke, with no benefit for the end point of death or myocardial infarction. In conclusion, β blockers are associated with an increased risk for new-onset DM, with no benefit for the end point of death or myocardial infarction and with a 15% increased risk for stroke compared with other agents. This risk was greater in patients with higher baseline body mass indexes and higher baseline fasting glucose levels and in studies in which β blockers were less efficacious antihypertensive agents compared with other treatments.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wolf-Maier K.
        • Cooper R.S.
        • Banegas J.R.
        • Giampaoli S.
        • Hense H.W.
        • Joffres M.
        • Kastarinen M.
        • Poulter N.
        • Primatesta P.
        • Rodriguez-Artalejo F.
        • et al.
        Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States.
        JAMA. 2003; 289: 2363-2369
        • National Institute of Diabetes and Digestive and Kidney Diseases
        National Diabetes Statistics Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2005.
        U.S. Department of Health and Human Services, National Institute of Health, Bethesda, Maryland2006
        • Gerber L.M.
        • Madhavan S.
        • Alderman M.H.
        Coincident hypertension.
        N Y State J Med. 1983; 83: 693-696
        • Pell S.
        • D’Alonzo C.A.
        Some aspects of hypertension in diabetes mellitus.
        JAMA. 1967; 202: 104-110
        • Alderman M.H.
        • Cohen H.
        • Madhavan S.
        Diabetes and cardiovascular events in hypertensive patients.
        Hypertension. 1999; 33: 1130-1134
        • Davey Smith G.
        • Bracha Y.
        • Svendsen K.H.
        • Neaton J.D.
        • Haffner S.M.
        • Kuller L.H.
        Incidence of type 2 diabetes in the randomized multiple risk factor intervention trial.
        Ann Intern Med. 2005; 142: 313-322
        • Dunder K.
        • Lind L.
        • Zethelius B.
        • Berglund L.
        • Lithell H.
        Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study.
        BMJ. 2003; 326: 681
        • Gress T.W.
        • Nieto F.J.
        • Shahar E.
        • Wofford M.R.
        • Brancati F.L.
        Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus.
        N Engl J Med. 2000; 342: 905-912
        • Lithell H.
        • Pollare T.
        • Vessby B.
        Metabolic effects of pindolol and propranolol in a double-blind cross-over study in hypertensive patients.
        Blood Press. 1992; 1: 92-101
        • Lithell H.O.
        Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism.
        Diabetes Care. 1991; 14: 203-209
        • Pepine C.J.
        • Handberg E.M.
        • Cooper-DeHoff R.M.
        • Marks R.G.
        • Kowey P.
        • Messerli F.H.
        • Mancia G.
        • Cangiano J.L.
        • Garcia-Barreto D.
        • Keltai M.
        • et al.
        A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease.
        JAMA. 2003; 290: 2805-2816
        • Berglund G.
        • Andersson O.
        • Widgren B.
        low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic.
        Acta Med Scand. 1986; 220: 419-424
        • Gurwitz J.H.
        • Bohn R.L.
        • Glynn R.J.
        • Monane M.
        • Mogun H.
        • Avorn J.
        Antihypertensive drug therapy and the initiation of treatment for diabetes mellitus.
        Ann Intern Med. 1993; 118: 273-278
        • Padwal R.
        • Laupacis A.
        Antihypertensive therapy and incidence of type 2 diabetes: a systematic review.
        Diabetes Care. 2004; 27: 247-255
        • Padwal R.
        • Mamdani M.
        • Alter D.A.
        • Hux J.E.
        • Rothwell D.M.
        • Tu K.
        • Laupacis A.
        Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort.
        Diabetes Care. 2004; 27: 2458-2463
        • Bradburn MJ D.J.
        • Altman D.
        Sbe24: metan—an alternative meta-analysis command.
        Stata Tech Bull Reprints. 1998; 8: 86-100
        • Galbraith R.F.
        A note on graphical presentation of estimated odds ratios from several clinical trials.
        Stat Med. 1988; 7: 889-894
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Wikstrand J.
        • Warnold I.
        • Tuomilehto J.
        • Olsson G.
        • Barber H.J.
        • Eliasson K.
        • Elmfeldt D.
        • Jastrup B.
        • Karatzas N.B.
        • Leer J.
        • et al.
        Metoprolol versus thiazide diuretics in hypertension.
        Hypertension. 1991; 17: 579-588
        • Wilhelmsen L.
        • Berglund G.
        • Elmfeldt D.
        • Fitzsimons T.
        • Holzgreve H.
        • Hosie J.
        • Hornkvist P.E.
        • Pennert K.
        • Tuomilehto J.
        • Wedel H.
        Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.
        J Hypertens. 1987; 5: 561-572
        • Kostis J.B.
        • Wilson A.C.
        • Freudenberger R.S.
        • Cosgrove N.M.
        • Pressel S.L.
        • Davis B.R.
        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
        • Lindholm L.H.
        • Persson M.
        • Alaupovic P.
        • Carlberg B.
        • Svensson A.
        • Samuelsson O.
        Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study).
        J Hypertens. 2003; 21: 1563-1574
        • Medical Research Council Working Party
        MRC Trial of Treatment of Mild Hypertension: principal results.
        BMJ (Clin Res Ed). 1985; 291: 97-104
        • MRC Working Party
        Medical Research Council Trial of Treatment of Hypertension in Older Adults: principal results.
        BMJ. 1992; 304: 405-412
        • Veterans Administration Cooperative Study Group on Antihypertensive Agents
        Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. II.
        JAMA. 1982; 248: 2004-2011
        • Dahlof B.
        • Devereux R.B.
        • Kjeldsen S.E.
        • Julius S.
        • Beevers G.
        • de Faire U.
        • Fyhrquist F.
        • Ibsen H.
        • Kristiannson K.
        • Lederballe-Pederson O.
        • et al.
        Cardiovascuar morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial of atenolol.
        Lancet. 2002; 359: 995-1003
        • Dahlof B.
        • Sever P.S.
        • Poulter N.R.
        • Wedel H.
        • Beevers D.G.
        • Caulfield M.
        • Collins R.
        • Kjeldsen S.E.
        • Kristinsson A.
        • McInnes G.T.
        • et al.
        Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.
        Lancet. 2005; 366: 895-906
        • Hansson L.
        • Hedner T.
        • Lund-Johansen P.
        • Kjeldsen S.E.
        • Lindholm L.H.
        • Syvertsen J.O.
        • Lanke J.
        • de Faire U.
        • Dahlof B.
        • Karlberg B.E.
        Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.
        Lancet. 2000; 356: 359-365
        • Hansson L.
        • Lindholm L.H.
        • Ekbom T.
        • Dahlof B.
        • Lanke J.
        • Schersten B.
        • Wester P.O.
        • Hedner T.
        • de Faire U.
        Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients With Hypertension-2 study.
        Lancet. 1999; 354: 1751-1756
        • Hansson L.
        • Lindholm L.H.
        • Niskanen L.
        • Lanke J.
        • Hedner T.
        • Niklason A.
        • Luomanmaki K.
        • Dahlof B.
        • de Faire U.
        • Morlin C.
        • et al.
        Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.
        Lancet. 1999; 353: 611-616
        • Thornley-Brown D.
        • Wang X.
        • Wright Jr, J.T.
        • Randall O.S.
        • Miller E.R.
        • Lash J.P.
        • Gassman J.
        • Contreras G.
        • Appel L.J.
        • Agodoa L.Y.
        • Cheek D.
        Differing effects of antihypertensive drugs on the incidence of diabetes mellitus among patients with hypertensive kidney disease.
        Arch Intern Med. 2006; 166: 797-805
        • Ferrannini E.
        • Buzzigoli G.
        • Bonadonna R.
        • Giorico M.A.
        • Oleggini M.
        • Graziadei L.
        • Pedrinelli R.
        • Brandi L.
        • Bevilacqua S.
        Insulin resistance in essential hypertension.
        N Engl J Med. 1987; 317: 350-357
        • Lissner L.
        • Bengtsson C.
        • Lapidus L.
        • Kristjansson K.
        • Wedel H.
        Fasting insulin in relation to subsequent blood pressure changes and hypertension in women.
        Hypertension. 1992; 20: 797-801
        • Taittonen L.
        • Uhari M.
        • Nuutinen M.
        • Turtinen J.
        • Pokka T.
        • Akerblom H.K.
        Insulin and blood pressure among healthy children.
        Am J Hypertens. 1996; 9: 194-199
        • Fajans S.S.
        • Floyd Jr, J.C.
        • Knopf R.F.
        • Rull J.
        • Guntsche E.M.
        • Conn J.W.
        Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.
        J Clin Invest. 1966; 45: 481-492
        • Sharma A.M.
        • Pischon T.
        • Hardt S.
        • Kunz I.
        • Luft F.C.
        Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis.
        Hypertension. 2001; 37: 250-254
        • Pollare T.
        • Lithell H.
        • Selinus I.
        • Berne C.
        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
        • Bakris G.L.
        • Fonseca V.
        • Katholi R.E.
        • McGill J.B.
        • Messerli F.H.
        • Phillips R.A.
        • Raskin P.
        • Wright Jr, J.T.
        • Oakes R.
        • Lukas M.A.
        • et al.
        Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.
        JAMA. 2004; 292: 2227-2236
        • Pitre M.
        • Gaudreault N.
        • Santure M.
        • Nadeau A.
        • Bachelard H.
        Isradipine and insulin sensitivity in hypertensive rats.
        Am J Physiol. 1999; 276: E1038-E1048
        • Deibert D.C.
        • DeFronzo R.A.
        Epinephrine-induced insulin resistance in man.
        J Clin Invest. 1980; 65: 717-721
        • Lithell H.
        Metabolic effects of antihypertensive drugs interacting with the sympathetic nervous system.
        Eur Heart J. 1992; 13: 53-57
        • Bosch J.
        • Yusuf S.
        • Gerstein H.C.
        • Pogue J.
        • Sheridan P.
        • Dagenais G.
        • Diaz R.
        • Avezum A.
        • Lanas F.
        • et al.
        • DREAM Trial Investigators
        Effect of ramipril on the incidence of diabetes.
        N Engl J Med. 2006; 355: 1551-1562
        • Zavaroni I.
        • Coruzzi P.
        • Bonini L.
        • Mossini G.L.
        • Musiari L.
        • Gasparini P.
        • Fantuzzi M.
        • Reaven G.M.
        Association between salt sensitivity and insulin concentrations in patients with hypertension.
        Am J Hypertens. 1995; 8: 855-858
        • Su H.Y.
        • Sheu W.H.
        • Chin H.M.
        • Jeng C.Y.
        • Chen Y.D.
        • Reaven G.M.
        Effect of weight loss on blood pressure and insulin resistance in normotensive and hypertensive obese individuals.
        Am J Hypertens. 1995; 8: 1067-1071
        • Giugliano D.
        • De Rosa N.
        • Di Maro G.
        • Marfella R.
        • Acampora R.
        • Buoninconti R.
        • D’Onofrio F.
        Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women.
        Diabetes Care. 1993; 16: 1387-1390
        • Ogihara T.
        • Rakugi H.
        • Ikegami H.
        • Mikami H.
        • Masuo K.
        Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives.
        Am J Hypertens. 1995; 8: 316-320
        • Eberly L.E.
        • Cohen J.D.
        • Prineas R.
        • Yang L.
        Impact of incident diabetes and incident nonfatal cardiovascular disease on 18-year mortality: the multiple risk factor intervention trial experience.
        Diabetes Care. 2003; 26: 848-854