Effects of candesartan cilexetil on glucose homeostasis. Multicenter Study Group

In a multicenter, randomized, double-blind, placebo-controlled clinical trial the effects of candesartan cilexetil (cand.cil.), a novel angiotensin II antagonist selective for the AT1 receptor with long-lasting antihypertensive activity, on glucose homeostasis--and the serum lipid profile--were assessed in patients with mild hypertension and stable type II diabetes mellitus. A total of 161 men and women, 30-75 years old, with mild hypertension (sitting diastolic blood pressure 90-100 mmHg) and type II diabetes (HbA1c 5.5-9.0%), both measured after a 4-week placebo run-in period, were randomized to double-blind treatment with cand.cil. 8 mg o.i.d. (n = 83) or placebo (n = 78). Dose was increased to 16 mg o.i.d., if diastolic blood pressure remained > or = 90 mmHg. At randomization and after 12 weeks of treatment HbA1c (primary effect variable), blood glucose and the serum lipid profile (including total cholesterol, HDL and LDL cholesterol, triglycerides) 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 HbA1c, blood glucose, and serum lipids compared to placebo. The median HbA1c both at baseline 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 the median difference in change between the groups was narrow (-0.25; 0.16), including zero, which excluded any clinically important difference. The same held true for blood glucose (-1.10; 0.20), total cholesterol (-0.40; 0.20), and the other lipid parameters. More than 60% of the patients reached a diastolic blood pressure < 90 mmHg; adverse events 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. for 12 weeks does not affect glucose homeostasis respectively serum lipids. Blood pressure was controlled in most patients and cand.cil. was well tolerated.