Time-line to use of incretin-based therapies in the treatment of diabetes
| Year | The Development of Incretin-Based Therapies |
|---|---|
| 1869 | Islets of Langerhans (nests of cells that appeared different from the surrounding pancreatic tissue) in the pancreas were described. |
| 1901 | The role of islets of Langerhans (what ultimately became known as an endocrine function) in diabetes was described. |
| 1902 | The role of a substance (called secretin) secreted by gut cells that stimulates the digestive juices for the pancreas (what ultimately became known as exocrine function) was described. |
| 1905 | This type of substance, a presumed “chemical messenger,” was now called a “hormone.” |
| 1906 | The role of a gut-derived hormone to treat diabetes was first alluded to. |
| 1921–1922 | Extraction of insulin from pancreas and its potential to treat type 1 diabetes was shown. |
| 1932 | The term “incretin” was used for the first time to refer to a substance derived from the gut, presumably a hormone, that regulates insulin secretion after eating. |
| 1960 | Radioimmunoassay was developed for measurement of plasma insulin levels. |
| 1964–1967 | Clinical proof that a gut-derived factor positively modulated insulin secretion. |
| 1971 | The first incretin, GIP, was isolated and sequenced. |
| 1985 | The second incretin, GLP-1, was described. |
| 1992–1994 | Studies show that exogenous GIP does not lower blood glucose in T2DM, but exogenous GLP-1 does so. |
| 2002 | Exendin-4, a GLP-1 receptor agonist extracted from Gila monster lizard saliva, was shown to powerfully stimulate insulin secretion in a glucose-dependent manner in subjects with and without T2DM. |
| 2005 | Exenatide (synthetic exendin-4) came into clinical use for T2DM. |
| 2006 | Sitagliptin, an orally active dipeptidyl peptidase 4 inhibitor, came into use in T2DM. |