Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control

Am J Hypertens. 2003 May;16(5 Pt 1):381-6. doi: 10.1016/s0895-7061(03)00062-1.


Background: There is evidence that diuretics and beta blockers impair glucose tolerance, whereas calcium channel blockers and angiotensin converting enzyme blockers lack this metabolic effect. We compared the effect of a combination therapy with a nondihydropyridine calcium channel blocker plus an angiotensin converting enzyme inhibitor and a beta blocker plus a diuretic on hemoglobin A(1c) (Hb A(1c)) in patients with type 2 diabetes and mild-to- moderate hypertension.

Methods: A total of 463 hypertensive outpatients with non-insulin treated type 2 diabetes on stable antidiabetic therapy for at least 3 months and with HbA(1c) between 6.5% and 10% were recruited. In a randomized, double blind trial patients were treated for 20 weeks with fixed combinations of verapamil sustained release (SR) plus trandolapril and of atenolol plus chlorthalidone following a 2-week placebo run-in period. The main outcome measures were HbA(1c), fasting plasma glucose, and fructosamine levels as well as systolic and diastolic blood pressure.

Results: HbA(1c) remained stable at 7.9% after administration of verapamil SR plus trandolapril and increased from 7.8% to 8.6% with atenolol plus chlorthalidone; the differences between treatment groups were significant at 4, 12, and 20 weeks of treatment and at last visit (P <.0001). Mean blood pressure fell from 169/96 to 150/85 and from 168/95 to 145/83 mm Hg after administration of verapamil SR plus trandolapril and atenolol plus chlorthalidone, respectively. Both combinations were well tolerated.

Conclusions: HbA(1c) and other parameters of short- and long-term glycemic control were in a more favorable range after antihypertensive treatment with verapamil SR plus trandolapril as compared with atenolol plus chlorthalidone.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Atenolol / therapeutic use*
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Chlorthalidone / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diastole / drug effects
  • Diuretics / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fasting / blood
  • Female
  • Glycated Hemoglobin A / drug effects
  • Heart Rate / drug effects
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Patient Compliance
  • Systole / drug effects
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use*
  • Verapamil / therapeutic use*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Biomarkers
  • Blood Glucose
  • Diuretics
  • Glycated Hemoglobin A
  • Indoles
  • Vasodilator Agents
  • trandolapril
  • Atenolol
  • Verapamil
  • Chlorthalidone