Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus

Research output: Contribution to journalJournal articleResearchpeer-review

J W Stephens, T B Bodvarsdottir, K Wareham, S L Prior, R M Bracken, G D Lowe, A Rumley, G Dunseath, S Luzio, C F Deacon, Jens Juul Holst, S C Bain

Aim: To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release, incretins, oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin.
Methods: A randomized clinical trial was performed recruiting 27 subjects (HbA1c between 7.5 and 10.5%) free from cardiovascular and renal disease. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), total antioxidant
status, F2-isoprostane, interleukin-6 and cell adhesion molecules were measured
during an oral glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC45, AUC60, AUC120).
Results: Significant improvements in glucose were observed with repaglinide (HBA1c: 1.5%, fasting glucose: 2.8 mmol/L, 2-h glucose: 3.7 mmol/L, AUC120: 18.9%) and glibenclamide (1.0%, 2.2 mmol/L, 2.5 mmol/L, 17.5%). Repaglinide was also associated with an increase in the AUC60 and AUC120 for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1,
GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1 and plasma markers of oxidative stress.
Conclusion: Repaglinide is associated with improved postprandial glycaemic control via insulin and C-peptide release. We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP. We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress.
Original languageEnglish
JournalDiabetes Research and Clinical Practice
Volume94
Issue number2
Pages (from-to)199-206
Number of pages8
ISSN0168-8227
DOIs
Publication statusPublished - Nov 2011

    Research areas

  • Adult, Aged, Analysis of Variance, Biological Markers, Blood Glucose, Carbamates, Diabetes Mellitus, Type 2, Drug Administration Schedule, Drug Therapy, Combination, E-Selectin, F2-Isoprostanes, Female, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Glyburide, Hemoglobin A, Glycosylated, Humans, Hyperglycemia, Hypoglycemic Agents, Incretins, Insulin, Intercellular Adhesion Molecule-1, Interleukin-6, Male, Metformin, Middle Aged, Oxidative Stress, Piperidines, Postprandial Period, Time Factors, Treatment Outcome, Wales

ID: 38186756