Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial

J Clin Endocrinol Metab. 2000 May;85(5):1882-9. doi: 10.1210/jcem.85.5.6599.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldosterone / blood
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Glucose / metabolism*
  • Blood Pressure
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy
  • Double-Blind Method
  • Female
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Heart Rate
  • Humans
  • Hyperinsulinism / blood
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Indoles / therapeutic use*
  • Insulin / pharmacology*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Placebos
  • Renin / blood

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Indoles
  • Insulin
  • Placebos
  • trandolapril
  • Aldosterone
  • Peptidyl-Dipeptidase A
  • Renin
  • Glucose