Trandolapril Does Not Improve Insulin Sensitivity in Patients with Hypertension and Type 2 Diabetes: A Double-Blind, Placebo-Controlled Crossover Trial1
John R. Petrie,
Andrew D. Morris,
Shinichiro Ueda,
Michael Small,
Richard Donnelly,
John M. C. Connell and
Henry L. Elliott
University Department of Medicine and Therapeutics (J.R.P., M.S.,
J.M.C.C., H.L.E.), Western Infirmary, West Glasgow Hospitals University
NHS Trust, Glasgow G11 6NT, United Kingdom; Department of
Medicine (A.D.M.), Ninewells Hospital and Medical School, University of
Dundee, Dundee DD1 954, United Kingdom; Second Department of
Medicine (S.U.), Yokohama City University School of Medicine, 3-9,
Fuku-ura, Kanazawa-ku, Yokohama 236, Japan; and School of Medical and
Surgical Sciences (R.D.), University of Nottingham, Derbyshire Royal
Infirmary, Derby DE1 2Q4 United Kingdom
Address correspondence and requests for reprints to: Dr. John R. Petrie, University Department of Medicine and Therapeutics, Western Infirmary, West Glasgow Hospitals University NHS Trust, Glasgow G11 6NT, United Kingdom. E-mail: jrp1s{at}clinmed.gla.ac.uk
Angiotensin-converting enzyme (ACE) inhibitors are increasinglyused as
first-line therapy for hypertension in type 2 diabetesmellitus and are
widely believed to improve insulin sensitivity(M). However, the
evidence for the latter effect does not standclose scrutiny. We have
assessed the effect of the ACE inhibitortrandolapril on M in 16
patients (mean ± SD age, 58 ±10.6 yr) with
mild-to-moderate essential hypertension (initialblood pressure,
173 ± 14.5/93 ± 8.0 mm Hg), obesity(body mass index,
30 ± 5.4 kg/m2), and impaired glucoseintolerance
(n = 4) or type 2 diabetes (n = 12) in a double-blind,
placebo-controlledcrossover design. All patients underwent three 3-h
euglycemichyperinsulinemic clamp studies (soluble insulin, 1.5
mU/kg·min)after a 2-week placebo run-in and at the end of two 4-week
periodsof 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 (trandolaprilvs. placebo); 95% power to
exclude an 8% increase in M. In conclusion,trandolapril had no
clinically relevant effect on M in patientswith hypertension and type
2 diabetes. Previous reports of improvedM during ACE inhibitor
treatment may be attributable to suboptimalstudy design and/or use of
surrogate measures of M.
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