Metabolic effects of lacidipine: a placebo-controlled study using the euglycaemic hyperinsulinaemic clamp

Abstract

1. Twelve healthy male volunteers received lacidipine 4 mg and matching placebo, each for 2 weeks, in a randomised, double‐blind crossover study, and attended on 4 study days to evaluate the effects of single and multiple dosing using the euglycaemic hyperinsulinaemic 'clamp'. 2. On each study day, a primed constant‐rate infusion of soluble insulin (1.5 mu kg‐1 min‐1) was administered for 180 min with a variable‐rate infusion of 20% dextrose to maintain euglycaemia (5.2 mmol l‐1). Whole‐body insulin sensitivity was calculated during the past 40 min of the 'clamp'. At frequent intervals, measurements of BP and HR were recorded and venous blood samples collected for serum insulin, C‐peptide, potassium, triglyceride (TG) and plasma noradrenaline concentrations. 3. Lacidipine was generally well tolerated and there were no adverse biochemical events. Mean values for insulin sensitivity +/‐ s.d. were 8.9 +/‐ 1.6 and 9.1 +/‐ 2.0 mg kg‐1 min‐1 after single doses of lacidipine and placebo respectively (95% CI, ‐1.0, 1.3), and correspondingly 9.6 +/‐ 2.1 and 9.7 +/‐ 1.5 mg kg‐1 min‐1 after 2 weeks (95% CI, ‐1.0, 1.3). 4. There was a significant reduction in fasting serum TG concentrations after 2 weeks of lacidipine: 0.7 +/‐ 0.3 mmol l‐1 vs 0.9 +/‐ 0.6 (P < 0.001). However, changes in serum TG and potassium concentrations during the 'clamp' were not significantly different between the 4 study days. 5. Thus, in 'insulin sensitive' volunteers, lacidipine reduces fasting serum TG concentrations but has no effect on insulin‐stimulated uptake of glucose, potassium and TG under euglycaemic hyperinsulinaemic conditions.