Timeline of incretin therapeutics (revision 12)
Old revision·05:32, 21 Jan 2025·INN_Ingrid
| Timeline of incretin therapeuticsReference material | |
|---|---|
| Span | 1900s to the present |
| Arrangement | Chronological |
| List infobox · conventions | |
This timeline sets out the development of incretin science and of the drugs derived from it, from the earliest observation that oral glucose provokes a larger insulin response than intravenous glucose, to the multi-receptor agonists in development.[1]
Dates are given for the events most consistently reported in the literature. Where a discovery is attributable to a series of publications rather than one, the timeline names the period rather than a single year.[2]
Approval dates are jurisdiction-specific; those given are for the first approval in a major market and may differ elsewhere. See Regulatory status by jurisdiction.[3]
Physiology
[edit]| Period | Event |
|---|---|
| 1900s–1920s | Observation that oral glucose evokes a larger insulin response than intravenous |
| 1960s | The term incretin revived; the enteroinsular axis proposed |
| 1970s | GIP isolated and characterised |
| 1980s | Glucagon-like peptide-1 identified as a proglucagon product and shown to be insulinotropic |
| 1986 | Reduced Incretin effect documented in type 2 diabetes |
| 1990s | Dipeptidyl peptidase-4 identified as the enzyme inactivating both incretins |
The 1986 finding is the hinge of the field: it established that the incretin axis is defective in type 2 diabetes and therefore a therapeutic target rather than only a physiological curiosity.[2]
Identification of DPP-4 as the inactivating enzyme defined the engineering problem every subsequent agonist solves. See GLP-1 receptor agonist.[1]
First-generation drugs
[edit]| Year | Event |
|---|---|
| 1990s | Exendin-4 identified in Gila monster venom |
| 2005 | Exenatide approved — first GLP-1 receptor agonist |
| 2006 | First DPP-4 inhibitor approved |
| 2009 | Liraglutide approved for type 2 diabetes |
| 2014 | Liraglutide approved for weight management |
| 2014 | Dulaglutide approved |
| 2016 | LEADER trial reports cardiovascular benefit |
The 2016 result changed the framing of the class from glucose-lowering to outcome-modifying, and it did so in a period when cardiovascular outcome trials were being run principally to exclude harm.[1]
See also
References
- ^ a b c Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." Cell Metabolism 27(4):740–756 (2018). PMID 29617641.
- ^ a b Holst JJ. "The physiology of glucagon-like peptide 1." Physiological Reviews 87(4):1409–1439 (2007). PMID 17928588.
- ^ American Diabetes Association. "Standards of Care in Diabetes." Diabetes Care 47(Suppl 1) (2024).