EFFECTS OF CANDESARTAN CILEXETIL ON GLUCOSE-HOMEOSTASIS

In a multicenter, randomized, double-blind, placebo-controlled clinica l trial the effects of candesartan cilexetil (cand.cil.), a novel angi otensin II antagonist selective for the AT(1) receptor with long-lasti ng antihypertensive activity, on glucose homeostasis - and the serum l ipid profile - were assessed in patients with mild hypertension and st able type II diabetes mellitus. A total of 161 men and women, 30-75 ye ars old, with mild hypertension (sitting diastolic blood pressure 90-1 00 mmHg) and type II diabetes (HbAlc 5.5-9.0 %), both measured after a 4-week placebo run-in period, were randomized to double-blind treatme nt with cand.cil. 8 mg o.i.d. (n = 83) or placebo (n = 78). Dose was i ncreased to 16 mg o.i.d., if diastolic blood pressure remained greater than or equal to 90 mmHg. At randomization and after 12 weeks of trea tment HbAlc (primary effect variable), blood glucose and the serum lip id profile (including total cholesterol, HDL and LDL cholesterol, trig lycerides) were assessed. The statistical analysis of the differences between treatments was based on changes from randomization to the end of the study. Cand.cil. had no significant effect on HbAlc, blood gluc ose, and serum lipids compared to placebo. The median HbAlc both at ba seline and after 12 weeks was 7.1 % in patients on cand.cil., and 7.2 % and 7.1 % in patients on placebo. The 95 % confidence interval for t he median difference in change between the groups was narrow (-0.25; 0 .16), including zero, which excluded any clinically important differen ce. The same held true for blood glucose (-1.10; 0.20), total choleste rol (-0.40; 0.20), and the other lipid parameters. More than 60 % of t he patients reached a diastolic blood pressure < 90 mmHg; adverse even ts and withdrawals were similar in both groups. Thus, in patients with mild hypertension and type II diabetes, cand.cil. 8 to 16 mg o.i.d. f or 12 weeks does not affect glucose homeostasis respectively serum lip ids. Blood pressure was controlled in most patients and cand.cil. was well tolerated.