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

John R. Petrie*, Andrew D. Morris, Shinichiro Ueda, Michael Small, Richard Donnelly, John M C Connell, Henry L. Elliott

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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/m 2), 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·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·min; placebo, 5.3 ± 1.70 mg/kg·min; trandolapril, 5.1 ± 1.65 mg/kg·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.

Original languageEnglish
Pages (from-to)1882-1889
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number5
DOIs
Publication statusPublished - 1 May 2000

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