Advertisement

Valsartan Inefficacy or Ill-Effects of Concomitant Medications!

      In the provocative review by the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) investigators,
      • Knowler W.C.
      • Barrett-Connor E.
      • Fowler S.E.
      • Hamman R.F.
      • Lachin J.M.
      • Walker E.A.
      • Nathan D.M.
      Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
      a single daily dose of valsartan reduced the risk for diabetes by 14% compared with placebo, a relative risk reduction lower than that see even with lifestyle modification in some trials. However, approximately 40% of patients were taking β blockers and 40% diuretics, agents that have been consistently shown to have adverse metabolic effects. In a meta-analysis of randomized trials of β blockers in patients with hypertension, treatment of 1,000 patients for 4.4 years resulted in 14 excess cases of diabetes.
      • Bangalore S.
      • Parkar S.
      • Grossman E.
      • Messerli F.H.
      A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus.
      Similarly, thiazide diuretics increased the risk for diabetes by 32% compared with placebo or non-β-blocker agents.
      • Messerli F.H.
      • Bangalore S.
      • Julius S.
      Risk/benefit assessment of beta-blockers and diuretics precludes their use for first-line therapy in hypertension.
      Conceivably, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, by mitigating hypokalemia associated with thiazide diuretics and by other effects, may abolish some of these adverse glycemic effects if given concomitantly with β blockers or diuretics. However, in the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR),
      • Bakris G.
      • Molitch M.
      • Hewkin A.
      • Kipnes M.
      • Sarafidis P.
      • Fakouhi K.
      • Bacher P.
      • Sowers J.
      Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome.
      in which patients with the metabolic syndrome were randomized to either verapamil and trandolapril or to losartan and hydrochlorothiazide, at the end of 1 year, losartan and hydrochlorothiazide increased plasma glucose significantly more than verapamil and trandolapril after all oral glucose tolerance testing. Similar results were documented in the International Verapamil-Trandolapril (INVEST) study and the Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) study.
      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

        • Knowler W.C.
        • Barrett-Connor E.
        • Fowler S.E.
        • Hamman R.F.
        • Lachin J.M.
        • Walker E.A.
        • Nathan D.M.
        Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
        N Engl J Med. 2002; 346: 393-403
        • Bangalore S.
        • Parkar S.
        • Grossman E.
        • Messerli F.H.
        A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus.
        Am J Cardiol. 2007; 100: 1254-1262
        • Messerli F.H.
        • Bangalore S.
        • Julius S.
        Risk/benefit assessment of beta-blockers and diuretics precludes their use for first-line therapy in hypertension.
        Circulation. 2008; 117: 2706-2715
        • Bakris G.
        • Molitch M.
        • Hewkin A.
        • Kipnes M.
        • Sarafidis P.
        • Fakouhi K.
        • Bacher P.
        • Sowers J.
        Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome.
        Diabetes Care. 2006; 29: 2592-2597