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Trandolapril Does Not Improve Insulin Sensitivity in Patients with Hypertension and Type 2 Diabetes: A Double-Blind, Placebo-Controlled Crossover Trial¹

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 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·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.

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