Effect of bezafibrate and colestyramine in patients with primary hypercholesterolemia.

40 patients with primary hypercholesterolemia were included in a randomized cross-over trial comparing effects and tolerance of bezafibrate (Cedur) (200 mg t.i.d.) and colestyramine (4 g t.i.d.). Gastrointestinal side-effects led to the discontinuation of colestyramine in 11 patients. No adverse events were observed with bezafibrate. Both drugs had similar effects on total and low density lipoprotein cholesterol (bezafibrate: -15% and -12%, respectively; colestyramine: -10% and -11%, respectively). While the high density lipoprotein-increasing effect of bezafibrate was more marked (+20% vs. +14%), triglycerides and very low density lipoprotein cholesterol were lowered by bezafibrate (-22% and -27%, respectively) and tended to increase with colestyramine (+11% and +10%, respectively). In the light of results of a multicenter primary prevention trial bezafibrate also should have a protective effect on coronary heart disease. This, however, has to be proven in longterm prospective trials.

Trial of sulfonylurea in combination with insulin in the therapy of diabetes type I and II. Evidence against a primary extrapancreatic receptor effect.

Recently in vitro evidence has been presented that sulfonylurea derivatives exert their chronic extrapancreatic effect by increasing the number of cellular insulin receptors. To ascertain if this receptor effect holds in vivo, we performed a randomized double-blind study on 21 type I (0.3 ng/ml residual C-peptide secretory capacity after glucose/glibenclamide stimulation), and on 19 insulin treated type II (2.0 ng/ml C-peptide) diabetics. The patients received for six weeks 10 mg/d of glibenclamide in addition to insulin. Insulin binding was initially lower in type II (4.7 +/- 0.75% per 10(7) monocytes and 6.39 +/- 1.08% per 4.5 X 10(9) erythrocytes) than in type I diabetic patients (5.1 +/- 0.48% and 7.95 +/- 0.88% respectively) and in 12 normal subjects (5.25 +/- 0.48 and 8.1 +/- 0.94% respectively). Glibenclamide normalized the number of monocyte receptors (from 4.14 to 5.49 X 10(4) sites/cell) in type II patients, but was without effect in type I diabetics. Blood glucose was significantly reduced (240 to 182 mg/dl; p = 0.02) in the type II group with a concomitant decrease in glycosylated hemoglobin from 12.4 to 10.5% (p = 0.01). Most of the effect occurred during the first week of treatment. Glibenclamide was the more effective the worse the initial metabolic state (r = -0.93; p = 0.001). Erythrocyte insulin receptors decreased markedly in both groups, perhaps due to a sulfonyl urea-induced change in erythrocyte plasma survival time. It is concluded that sulfonylurea treatment is a valuable adjunct in reducing the insulin resistance in insulin treated type II diabetics. The effect depends on the availability of endogenous insulin, thus exhibiting only partly extrapancreatic character.(ABSTRACT TRUNCATED AT 250 WORDS)