Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists or incretin mimetics, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes.[1][2] One of their advantages over older insulin secretagogues, such as sulfonylureas or meglitinides, is that they have a lower risk of causing hypoglycemia.[3] GLP-1 has a short duration of action, so to overcome this limitation several modifications either in the drug or the formulations are being developed. [4]
There is some dispute over the safety profile of these drugs due to proliferative effects in the pancreas.[citation needed] Diabetes is associated with both acute pancreatitis and pancreatic cancer. While some recent studies have not found that these drugs can cause either pancreatitis or cancer,[5] a 2017 study found that recent prescription of incretins was associated with an increased risk of pancreatic cancer over non-insulin anti diabetic drugs (NIADs).[6]
Health effects
As of 2017 it was unclear if they affect a person's risk of death.[7] A JAMA article meta-analysis in 2018 (covering studies concerning GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors) showed GLP-1 agonists were associated with lower stroke risk than controls.[8]
Approved
- exenatide (Byetta, Bydureon), approved in 2005/2012
- liraglutide (Victoza, Saxenda), approved 2010[9]
- lixisenatide (Lyxumia in Europe, Adlyxin in the United States), approved in 2016[10]
- albiglutide (Tanzeum), approved in 2014 by GSK[11]
- dulaglutide (Trulicity), approved in 2014—manufactured by Eli Lilly[12]
- semaglutide (Ozempic, Rybelsus), approved in 2017.[13]
Under investigation
- taspoglutide, phase III halted Sept 2010[1]
Mechanism
These agents work by activating the GLP-1R, rather than inhibiting the breakdown of GLP-1 as do DPP-4 inhibitors, and are generally considered more potent.[14]
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