In a randomized, double-blind study (n=58) with parallel groups, the effects of diltiazem (mean dose 329mg/day) and atenolol (mean dose 67mg/day) on carbohydrate and lipoprotein metabolism in hypertensive patients were compared. The mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) reductions in the supine position were similar and satisfactory, 9/11 and 11/9 mmHg during atenolol and diltiazem treatment, respectively. Insulin-mediated glucose uptake, measured with the euglycaemic insulin clamp technique, decreased during atenolol treatment, from 7.1 to 5.6mg/kg per min (P=0.005) but not during treatment with diltiazem (initial value 6.8, final value 6.7mg/kg per min;P> 0.8). Treatment differences between groups were statistically significant (P< 0.05).During atenolol treatment there was a slight but significant increase in plasma glucose in the fasting state (P<0.05) and at the end of an intravenous glucose tolerance test (IVGTT;P< 0.01), and in plasma insulin at the end of IVGTT (P< 0.05). Despite increased insulin resistance the increase in insulin response was small, suggesting inhibition of insulin release. The insulin peak was decreased by 13% during diltiazem treatment (P < 0.05). The concentrations of very-low- and low-density lipoprotein triglycerides increased, whereas high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol was unaffected during atenolol treatment. In conclusion, there was no difference between the antihypertensive effects of atenolol and diltiazem, but atenolol decreased insulin sensitivity and altered the lipid profile, thus possibly increasing the risk of diabetes mellitus and theoretically reducing the benefits of blood pressure reduction with regard to risk of coronary heart disease.