INSULIN SENSITIVITY FOLLOWING TREATMENT WITH THE ALPHA(1)-BLOCKER BUNAZOSIN RETARD AND THE BETA(1)-BLOCKER ATENOLOL IN HYPERTENSIVE NON-INSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS

Objective To compare the effects of the alpha(1)-blocker bunazosin ret ard and the beta(1)-blocker atenolol (Uniloc) on insulin sensitivity a nd glucose and lipid homeostasis in patients with type-2 diabetes and hypertension. Methods Patients with controlled type-2 diabetes (nonins ulin-dependent diabetes mellitus), treated by diet or oral sulphonylur ea derivatives, and with mild-to-moderate hypertension were included i n a randomized, parallel group, double-blind, multicentre study, After a single-blind placebo run-in period lasting 4-6 weeks, the patients were treated either with bunazosin retard or with atenolol for a furth er 16 weeks including an initial dose titration period to achieve bloo d pressure control. Treatment involved 3, 6 or 12 mg bunazosin retard tablets or 25, 50 or 100 mg atenolol tablets, administered orally once a day and prescribed according to blood pressure response. The euglyc aemic hyperinsulinaemic clamp technique was used to assess insulin sen sitivity both after the placebo period and after the active treatment. A total of 95 patients was enrolled in the study (placebo phase), For ty-eight patients were withdrawn from the placebo phase, mainly due to their blood pressures being outside the required range (seated diasto lic blood pressure 90-114 mmHg) and 47 patients were allocated randoml y to active treatment Of these, 23 were administered bunazosin retard and 24 atenolol, All evaluations were on an intention-to-treat basis. Results insulin sensitivity assessed as glucose utilization during the cramp was significantly higher following bunazosin retard compared wi th following atenolol administration (3.52+/-0.27 versus 2.86+/-0.19 u nits of metabolic clearance rate of glucose index, P<0.05). The insuli n lever attained during cramps (infusion rate 56 mU/m(2) per min) was higher (P<0.05) following atenolol (117+/-5 mU/l) than it was followin g bunazosin retard administration (102+/-5) or placebo (108+/-3), poss ibly due to an impaired insulin clearance. Compared with placebo, aten olol treatment resulted in significantly increased glucosylated haemog lobin whereas bunazosin retard had no significant effect. The two drug s did not show any consistent differences in lipid profile or fibrinog en and plasminogen activator inhibitor 1 levels. During the study seve n serious adverse events were reported and one was reported shortly af ter completion of the study, All except one were classified as not rel ated to the study drug and five of them occurred during placebo treatm ent The non-serious side effects were in general considered to be eith er unrelated to the test drugs or expected effects of the two respecti ve drug classes, Both bunazosin retard and atenolol displayed acceptab le safety profiles. Conclusion Bunazosin retard treatment in hypertens ive non-insulin-dependent diabetes mellitus patients appears to be ass ociated with a slightly higher insulin sensitivity than is atenolol.