The effect of glibenclamide on insulin secretion at normal glucose concentrations

Axel Riefflin; Usha Ayyagari; Susan E. Manley; Rury R. Holman; Jonathan C. Levy

doi:10.1007/s00125-014-3399-1

The effect of glibenclamide on insulin secretion at normal glucose concentrations

Axel Riefflin, Usha Ayyagari, Susan E. Manley, Rury R. Holman, Jonathan C. Levy

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Aims/hypothesis: The aim of this study was to investigate the incremental and proportional effect of a sulfonylurea on insulin secretion rates at low, elevated and high blood glucose, using parallel groups with ascending or descending glucose steps to minimise potential biases of a single stepped clamp order.

Methods: Following 14 days on placebo or glibenclamide (2.5 mg) tablets twice daily, separated by 14 days washout, 19 type 2 diabetic patients had ascending or descending three-step hyperinsulinaemic glucose clamps at 4, 8 and 12 mmol/l. C-peptide secretion was estimated by two-compartment C-peptide deconvolution.

Results: Patients in the ascending glucose steps group (n = 10) had mean (SD) age of 60.3 (6.5) years, BMI of 29.8 (4.9) kg/m² and fasting glucose on diet alone of 10.6 (2.9) mmol/l; while those in the descending glucose steps group (n = 9) had mean age of 58.2 (8.0) years, BMI of 30.5 (5.4) kg/m² and fasting glucose on diet alone of 9.8 (2.2) mmol/l. The geometric means (95% CI) of C-peptide secretion rates on placebo for glucose at 4.0, 8.0 and 12.0 mmol/l were 63 (46, 86), 143 (105, 195) and 205 (149, 281) pmol/min, respectively. On glibenclamide, this increased by 140 (99, 181), 126 (85, 167) and 158 (117, 199) pmol/min, respectively (p < 0.001 vs placebo). The absolute increment was significant (p < 0.001) and independent of clamp glucose concentration (p = 0.54). The proportional increase was greater at 4 mmol/l: 2.8-fold (2.4, 3.2), compared with 1.8-fold (1.5, 2.0) and 1.7-fold (1.4, 1.9) at 8 and 12 mmol/l, respectively (p < 0.001).

Conclusions/interpretation: At low-normal glucose, glibenclamide exerted a disproportionate effect on insulin secretion. This study highlights the risks of hypoglycaemia when aiming for tight glucose control on this agent.

Original language	English
Pages (from-to)	43-49
Number of pages	7
Journal	Diabetologia
Volume	58
Issue number	1
DOIs	https://doi.org/10.1007/s00125-014-3399-1
State	Published - Jan 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.

Funding

We would like to thank I. Stratton (Gloucestershire Diabetic Retinopathy Research Group, Gloucester, UK) for power calculations; B. Barrow, N. Walraevens and C. Dudley for nursing support, and P. Sutton for supervision of immunoassays (Diabetes Trials Unit, Oxford UK). The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This study was supported by a grant from Knoll Pharmaceuticals.

Funders	Funder number
Knoll Pharmaceuticals
National Institute for Health Research

Keywords

C-peptide secretion
Glibenclamide
Glyburide
Insulin secretion
Sulfonylurea
Type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-014-3399-1

Cite this

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abstract = "Aims/hypothesis: The aim of this study was to investigate the incremental and proportional effect of a sulfonylurea on insulin secretion rates at low, elevated and high blood glucose, using parallel groups with ascending or descending glucose steps to minimise potential biases of a single stepped clamp order.Methods: Following 14 days on placebo or glibenclamide (2.5 mg) tablets twice daily, separated by 14 days washout, 19 type 2 diabetic patients had ascending or descending three-step hyperinsulinaemic glucose clamps at 4, 8 and 12 mmol/l. C-peptide secretion was estimated by two-compartment C-peptide deconvolution.Results: Patients in the ascending glucose steps group (n = 10) had mean (SD) age of 60.3 (6.5) years, BMI of 29.8 (4.9) kg/m2 and fasting glucose on diet alone of 10.6 (2.9) mmol/l; while those in the descending glucose steps group (n = 9) had mean age of 58.2 (8.0) years, BMI of 30.5 (5.4) kg/m2 and fasting glucose on diet alone of 9.8 (2.2) mmol/l. The geometric means (95% CI) of C-peptide secretion rates on placebo for glucose at 4.0, 8.0 and 12.0 mmol/l were 63 (46, 86), 143 (105, 195) and 205 (149, 281) pmol/min, respectively. On glibenclamide, this increased by 140 (99, 181), 126 (85, 167) and 158 (117, 199) pmol/min, respectively (p < 0.001 vs placebo). The absolute increment was significant (p < 0.001) and independent of clamp glucose concentration (p = 0.54). The proportional increase was greater at 4 mmol/l: 2.8-fold (2.4, 3.2), compared with 1.8-fold (1.5, 2.0) and 1.7-fold (1.4, 1.9) at 8 and 12 mmol/l, respectively (p < 0.001).Conclusions/interpretation: At low-normal glucose, glibenclamide exerted a disproportionate effect on insulin secretion. This study highlights the risks of hypoglycaemia when aiming for tight glucose control on this agent.",

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AU - Levy, Jonathan C.

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N2 - Aims/hypothesis: The aim of this study was to investigate the incremental and proportional effect of a sulfonylurea on insulin secretion rates at low, elevated and high blood glucose, using parallel groups with ascending or descending glucose steps to minimise potential biases of a single stepped clamp order.Methods: Following 14 days on placebo or glibenclamide (2.5 mg) tablets twice daily, separated by 14 days washout, 19 type 2 diabetic patients had ascending or descending three-step hyperinsulinaemic glucose clamps at 4, 8 and 12 mmol/l. C-peptide secretion was estimated by two-compartment C-peptide deconvolution.Results: Patients in the ascending glucose steps group (n = 10) had mean (SD) age of 60.3 (6.5) years, BMI of 29.8 (4.9) kg/m2 and fasting glucose on diet alone of 10.6 (2.9) mmol/l; while those in the descending glucose steps group (n = 9) had mean age of 58.2 (8.0) years, BMI of 30.5 (5.4) kg/m2 and fasting glucose on diet alone of 9.8 (2.2) mmol/l. The geometric means (95% CI) of C-peptide secretion rates on placebo for glucose at 4.0, 8.0 and 12.0 mmol/l were 63 (46, 86), 143 (105, 195) and 205 (149, 281) pmol/min, respectively. On glibenclamide, this increased by 140 (99, 181), 126 (85, 167) and 158 (117, 199) pmol/min, respectively (p < 0.001 vs placebo). The absolute increment was significant (p < 0.001) and independent of clamp glucose concentration (p = 0.54). The proportional increase was greater at 4 mmol/l: 2.8-fold (2.4, 3.2), compared with 1.8-fold (1.5, 2.0) and 1.7-fold (1.4, 1.9) at 8 and 12 mmol/l, respectively (p < 0.001).Conclusions/interpretation: At low-normal glucose, glibenclamide exerted a disproportionate effect on insulin secretion. This study highlights the risks of hypoglycaemia when aiming for tight glucose control on this agent.

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The effect of glibenclamide on insulin secretion at normal glucose concentrations

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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