Hormonal and metabolic effects of chlorpropamide, glibenclamide and placebo in a cross-over study in diabetics not controlled by diet alone

Abstract

Twenty diabetic patients, whose hyperglycaemia had been shown to fail to respond to at least one month's dietary treatment, completed a crossover study in order to: 1) compare the effectiveness of two sulphonylureas, chlorpropamide and glibenclamide, and 2) study the effects of sulphonylureas on insulin secretion and on biochemical indices of glucose intolerance. Fasting blood glucose fell on active treatment from 10.7 _-2 0.6 (mean _.+ SEM) to 6.6 + 0.7 mmol/l and rose again to 10.6 z 0.7 after 4 months placebo. A second period of 4 months sulphony/urea therapy resulted in a comparable fatl in blood glucose (to 6.9 + 0.7 mmol/1) and 'a similar relapse was seen after the second placebo period (to 10.5 ___ 0.9 mmol/i). Glucose tolerance and associated insulin secretion improved markedly on active treatment, with ketone bodies, non-esterified fatty acids, and glycerol falling to within the reference range. Sulphonylurea therapy was associated with a small but significant increase in the fasting insulin level. These effects were nearly all reversed 4 months after withdrawal of the sulphonylureas. No marked changes were found in growth hormone, lactate, pyruvate, lactate/pyruvate ratio or fasting cholesterol, trigtycerides and lipoproteins. On a weight basis, glibenclamide was 26 times more potent than chlorpropamide and, in the doses used in this study, their biochemical effects were indistinguishable. The effects of these two sulphonylureas seem most likely to be mediated by a direct stimulation of insulin secretion by the B-cell.

Sulphonylurea therapy doubles B-cell response to glucose in Type 2 diabetic patients

“…Although some studies show enhanced insulin responses [1][2][3][4], others have suggested that fasting and stimulated plasma insulin levels do not change during the chronic administration of sulphonylurea therapy [5][6][7][8][9][10][11]. These studies have not taken into account that the same plasma insulin, stimulated by a lower post-sulphonylurea-treatment plasma glucose level, may represent an improvement in B-cell function.…”

Glyburide and Glipizide in Treatment of Diabetic Patients With Secondary Failures to Tolazamide or Chlorpropamid

“…Because glyburide has stronger pharmacologic effects compared with tolbutamide (5,9), it is conceivable to achieve an improved metabolic control by switching from tolbutamide to glyburide. Sonksen et al (10) compared the effects of chlorpropamide and glyburide with oral glucose tolerance tests in 20 diabetic patients who could not be controlled with diet alone. There were no significant differences in the effects of the two drugs.…”

The Relationship Between the Pharmacokinetics and Pharmacodynamic Effects of Oral Hypoglycaemic Drugs

“…A careful placebo-controlled, open crossover study of chlorpropamide and glibenclamide in 20 diabetic subjects unresponsive to diet (Sonksen et al 1981) failed to show any significant difference in the effects of the two drugs on oral glucose tolerance. A more recent study (Prosser et al 1985) compared the effects of glibenclamide and chlorpropamide on 24-hour glucose and insulin profiles in diet-treated diabetic subjects before and after 4 months of drug therapy.…”

“…However, several studies (Hecht et al 1973;Hosker et al 1985;Judzewitsch et al 1982;Sonksen et al 1981) have shown increased responses. The study by Hosker et al (1985) which used the hyperglycaemic clamp technique to study glucosestimulated insulin release, is especially convincing, although only 6 of the 10 subjects received chlorpropamide and 4 received glibenclamide.…”