INSULIN SENSITIVITY IN A LONG-TERM CROSSOVER TRIAL WITH CELIPROLOL AND OTHER ANTIHYPERTENSIVE AGENTS

The effects of a vasodilating beta-blocker, celiprolol, on insulin sen sitivity and cardiovascular risk factors were compared with those of a nother beta(1)-selective adrenoceptor blocker, calcium channel blocker s, and angiotensin-converting enzyme (ACE) inhibitors. A randomized 21 -month crossover trial was carried out with 25 patients with dyslipide mia receiving antihypertensive monotherapy. The study consisted of a 3 -month active run-in period and two treatment periods, during which th e patients received celiprolol (200-400 mg daily) or the control drug for 12 and 6 months in a crossover manner. A hyperinsulinemic euglycem ic clamp and an oral glucose tolerance test (OGTT) were performed ever y 6 months. According to the clamp tests, the insulin-sensitivity inde x increased on average by 32% (p < 0.0001) during celiprolol treatment compared with that with the other antihypertensive agents, including ACE inhibitors. In OGTT, area under the incremental glucose curve decr eased by 36% (p = 0.002) during celiprolol treatment, whereas insulin secretion diminished on average by 26% (p = 0.006). The mean decrease in fasting serum triglycerides was 11% (NS), whereas the high-density lipoprotein to low-density lipoprotein (HDL/LDL) ratio increased by 15 % (p = 0.012). The results suggest that celiprolol improves insulin se nsitivity of hypertensive patients with dyslipidemia in long-term ther apy.