Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes

Diabetes Obes Metab. 2001 Dec;3(6):403-9. doi: 10.1046/j.1463-1326.2001.00152.x.


Objective: To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses.

Material and methods: Fifty patients with type 2 diabetes on regular Gb therapy (1.75-14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z-test (correlation coefficients) and paired Student t-tests were used when comparing values within the entire group and unpaired non-parametric Mann-Whitney tests were used when comparing high and low dose levels. A p-value < 0.05 was considered significant.

Results: There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), Delta-insulin (r = - 0.59) and Delta-proinsulin (r = - 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = - 0.40) and proinsulin (r = - 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on > or = 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0-120) and 33 (0-120) ng/ml) than those of Gb itself (18(0-64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen.

Conclusions: Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired beta-cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biotransformation
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Glyburide / blood
  • Glyburide / pharmacokinetics
  • Glyburide / therapeutic use*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Middle Aged
  • Proinsulin / blood*
  • Proinsulin / metabolism
  • Sweden
  • White People


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Proinsulin
  • Glyburide