Incretin mimetics
Incretins are insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are Glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent Insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Glucagon-like peptide (GLP) analogs
GLP agonists bind to a membrane GLP receptor. As a consequence of this, Insulin release from the pancreatic beta cells is increased. Endogenous GLP has a half life of only a few minutes; thus an analogue of GLP would not be practical.
- Exenatide (also Exendin-4, marketed as Byetta) is the first GLP agonist
approved for the treatment of type 2 diabetes. Exenatide is not an analogue
of GLP, but rather a GLP agonist.[citation needed] Exenatide has only a 53%
homology with GLP, which increases its resistance to degradation by DPP-4 and
extends its half-life.
- Liraglutide is being developed by Novo Nordisk. As of 2007, it is in phase
III clinical trials.
Gastric inhibitory peptide (GIP) analogs
- None are FDA approved
DPP-4 inhibitors
Main article: Dipeptidyl peptidase-4 inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 (glucagon-like peptide-1) by inhibiting its degradation by dipeptidyl peptidase-4 (DPP-4). Examples are:
- vildagliptin
- sitagliptin
Amylin analogues
Amylin agonist analogues slow gastric emptying and suppress glucagon. As of 2007, pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea, which occurs mostly at the beginning of treatment and gradually reduces.