Kinetics-Effect Relations of Insulin-Releasing Drugs in Patients With Type 2 Diabetes

Brief Overview

  1. Arne Melander
  1. From the the NEPI Foundation, Medical Research Center, Malmö University Hospital, Malmö, Sweden; and the Department of Community Medicine, Lund University, Lund, Sweden
  1. Address correspondence and reprint requests to Professor Arne Melander, MD, PhD, The NEPI Foundation, Medical Research Center, Malmö University Hospital (Entr: 59), SE-205 02 Malmö, Sweden. E-mail: arne.melander{at}


Sulfonylureas and glinides have similar mechanisms of action but differ in receptor affinity and binding sites and in absorption and elimination rates. This promotes differences in potency, rate of onset, and duration of action. While prominent in single-dose studies, these differences have less importance during long-term sulfonylurea treatment: at ordinary dosages, rapid- and short-acting (glipizide) and slow- and long-acting (glyburide) sulfonylureas maintained continuously effective plasma levels and similar 24-h glucose control. Moreover, there was no difference in patient outcome between the first-generation sulfonylurea chlorpropamide and the second-generation glyburide in the U.K. Prospective Diabetes Study. However, the risk of long-lasting and hence dangerous hypoglycemia is higher with these two long-acting sulfonylureas. Conversely, this risk should be low with the short-acting glinides, but seemingly at the expense of less effective glucose control. The most important kinetics-effect relations are that hyperglycemia delays sulfonylurea absorption and that the sulfonylurea dose-response curve is bell shaped; continuous sulfonylurea exposure over a certain level (e.g., 10 mg glipizide) impairs rather than improves insulin and glucose responses to sulfonylurea (downregulation). Accordingly, a vicious circle may be established: unrelenting hyperglycemia may promote sulfonylurea dose increase, which increases hyperglycemia, promoting further dose increase and eventually therapeutic failure.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted June 7, 2004.
    • Received March 10, 2004.
| Table of Contents