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

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as fir st-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 o f the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 /- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pre ssure, 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 u nderwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insul in, 1.5 mU/kg min) after a a-week placebo run-in and at the end of two 4-we ek periods of treatment with 2 mg trandolapril or placebo (a-week washout). M (mean +/- so) 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 (trandolapri l vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, tr andolapril had no clinically relevant effect on M in patients with hyperten sion and type 2 diabetes. Previous reports of improved M during ACE inhibit or treatment may be attributable to suboptimal study design and/or use of s urrogate measures of M.