Metabolic and Clinical Effects of Glibenclamide

Davidson, Margaret E; Lewis, Al; Mowbray, R.R. De; Boucher, B. J.; Oakley, N. W.; Nabarro, J. D. N.; Ginsburg, Jean; Beaconsfield, Peter

doi:10.1016/s0140-6736(70)91844-1

Cited by 25 publications

(11 citation statements)

References 8 publications

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“…In our patients, these measurements gave no more information on diabetic control than did the measurements of glucose alone. Results of such measurements after sulphonylureas by other workers have been in agreement with those reported here: a fall in NEFA [35], no change in hGH [23][24][25], and no change in lactate or pyruvate [24]. Abramson and Arky [15] found sulphonylurea treatment to be accompanied by a fall in cholesterol, but their patients were obese and had been started on diet and a sulphonylurea simultaneously.…”

Section: Discussionsupporting

confidence: 91%

“…Some authors have described, as we have, an increase in insulin concentrations after sulphonylureas [15][16][17][18][19][20][21][22] although some workers have noted an initial increase followed by a decrease in plasma insulin concentrations [17,18,21,23]. Other studies have found insulin to be unchanged [24][25][26][27], although transient early increases in insulin secretion were found in two of these studies [25,27]. Some workers have described a diminished insulin response to oral glucose after sulphonylureas [28][29][30].…”

Section: Discussionmentioning

confidence: 70%

“…Since in vitro and acnte in vivo studies in normal subjects have shown that tolbutamide stimulated insulin secretion, it was assumed that the hypoglycaemic effect of the drug in chronic diabetes was also mediated by increased insulin secretion. However some studies have shown improvement of glucose intolerance, without inereased insulin secretion [23][24][25][26][27]31], suggesting extra-pancreatic effects of sulphonylurea. These drugs are known to affect, in vitro, tissues other than the pancreatic B-cell [37], although mosf of these effects have been observed at drug concentrations (1250 mmol/1) [38,39], greatly in excess of those found in the plasma of sulphonylurea-treated diabetics (0.2-0.7 mmol/1) [31,40,41].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1981

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Summary. 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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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

et al. 1981

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“…[39][40][41][42] Phytochemical screening of CLEt revealed the presence of alkaloids, flavonoids, saponins, tannins, phenols, and cardiac glycosides. These phytochemicals as well as several plant extracts containing such chemical compounds have been shown to be endowed with antidiabetic potential.…”

Section: Effect On Glycogen Contentmentioning

confidence: 99%

Elucidation of Mechanism of Action ofCassia auriculataLeaf Extract for Its Antidiabetic Activity in Streptozotocin-Induced Diabetic Rats

Gupta

Sharma

Singh

et al. 2010

Journal of Medicinal Food

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Cassia auriculata traditionally has been used to treat diabetes from ancient times. The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of C. auriculata (CLEt) in streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) rats. CLEt was orally administered to MD and SD rats at a dose of 400 mg/kg once a day for 15 days. CLEt-treated MD and SD rats showed significant reduction in fasting blood glucose. Assessment of plasma insulin and C-peptide following treatment with CLEt revealed significant elevation in their levels. Administration of CLEt enhanced the activity of hepatic hexokinase and phosphofructokinase and suppressed glucose-6-phosphatase and fructose-1,6-bisphosphatase in both MD and SD rats. A significant rise in glycogen content was also observed in both liver and muscles of CLEt-fed MD and SD rats. Histopathological examination of pancreatic sections revealed increased number of islets and beta-cells in CLEt-treated MD as well as SD rats. The findings of the study suggest that the antidiabetic effect of CLEt could be due to its insulinogenic action. In addition, impaired glucose homeostasis was improved by feeding the extract through amelioration in the carbohydrate metabolic pathways. Thus, the extract may exert an antidiabetic effect through pancreatic as well as extrapancreatic action.

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“…In these studies, monitoring was continued for only 90 minutes, at which time blood glucose was 20% below predose levels. 15 hours after a single dose of glibenclamide in healthy volunteers, the hyperglycaemic response to oral glucose loading was reduced (Davidson et al 1970). After treatment with glibenclamide for up to 16 months, a single dose with breakfast maintained blood glucose control throughout the day in 30 diabetics (O'Sullivan & Cashman 1970).…”

Section: Patient Studiesmentioning

confidence: 99%

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

Ferner

Chaplin

1987

Clinical Pharmacokinetics

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Oral hypoglycaemic drugs have widely differing pharmacokinetic properties. Possible pharmacodynamic benefits include greater efficacy and fewer adverse effects. In general, it has not been possible to demonstrate unequivocal differences in clinical efficacy between the sulphonylureas during long term use, although there are clear differences in potency. These differences have been emphasised to the extent that the term 'second-generation' has been used for the most potent sulphonylureas, but there is little to suggest that potency is of any therapeutic significance. Trials to study differences in efficacy have rarely been of acceptable design. They have often used fixed doses of drugs, begging the question of whether true potency ratios have been established for chronic treatment. They have rarely involved substantial numbers of patients in double-blind crossover studies with a suitable washout period. Trials which show that there is a clear relationship between drug concentrations in blood and drug effects (whether therapeutic effects or adverse effects such as severe hypoglycaemia) are generally lacking. Qualitative and semiquantitative analysis of adverse effects supports the concept that drugs with a long half-life (e.g. chlorpropamide), renally excreted active metabolites (e.g. acetohexamide) or unusual properties (e.g. glibenclamide, which accumulates progressively in islet tissue) are more likely to cause prolonged hypoglycaemia, which may be fatal. The major adverse effect of treatment with biguanides is lactic acidosis, and this probably occurs more commonly in patients treated with phenformin than those treated with metformin because of pharmacogenetic variation in phenformin metabolism. The available evidence therefore favours the use of drugs with a short elimination half-life which are extensively metabolised and which have no active metabolites.

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Metabolic and Clinical Effects of Glibenclamide

Cited by 25 publications

References 8 publications

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

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

Elucidation of Mechanism of Action ofCassia auriculataLeaf Extract for Its Antidiabetic Activity in Streptozotocin-Induced Diabetic Rats

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

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