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Kinetics-effect relations of insulin-releasing drugs in patients with type 2 diabetes

Melander, Arne LU (2004) In Diabetes 53(Suppl.). p.151-155
Abstract
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... (More)
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 sulfanylurea dose increase, which increases hyperglycemia, promoting further dose increase and eventually therapeutic failure. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
53
issue
Suppl.
pages
151 - 155
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000225460000023
  • scopus:9444283277
ISSN
1939-327X
DOI
10.2337/diabetes.53.suppl_3.S151
language
English
LU publication?
yes
id
07445ca1-be86-4b97-98bf-c49f3a69cd34 (old id 259729)
alternative location
http://diabetes.diabetesjournals.org/cgi/content/abstract/53/suppl_3/S151
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15561903&dopt=Abstract
date added to LUP
2007-10-28 14:47:09
date last changed
2017-09-10 04:32:41
@article{07445ca1-be86-4b97-98bf-c49f3a69cd34,
  abstract     = {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 sulfanylurea dose increase, which increases hyperglycemia, promoting further dose increase and eventually therapeutic failure.},
  author       = {Melander, Arne},
  issn         = {1939-327X},
  language     = {eng},
  number       = {Suppl.},
  pages        = {151--155},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Kinetics-effect relations of insulin-releasing drugs in patients with type 2 diabetes},
  url          = {http://dx.doi.org/10.2337/diabetes.53.suppl_3.S151},
  volume       = {53},
  year         = {2004},
}