Glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or incretin mimetics, are

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s of the

GLP-1 receptor The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by ...

. This class of medications is used for the treatment of type 2 diabetes Some drugs are also approved for obesity. One of their advantages over older insulin secretagogues, such as sulfonylureas or meglitinides, is that they have a lower risk of causing hypoglycemia. GLP-1 has a short duration of action, so to overcome this limitation several modifications in either the drugs or the formulations are being developed. The 2022 ADA standards of medical care in diabetes include GLP-1-RA as a first line pharmacological therapy for type 2 diabetes, specifically in patients with atherosclerotic cardiovascular disease or obesity.

Health effects

A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcomes. 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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

risk than controls. Preclinical research has suggested the possibility that the drugs may increase the risk of pancreatitis and pancreatic cancer. Analyses of human trials have not found an increased risk of pancreatitis but are insufficiently powered to rule out an effect on pancreatic cancer. Studies in rodents have shown GLP1 mediated thyroid c-cell hyperplasia. A 2020 Cochrane systematic review did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal myocardial infarction, non-fatal

end-stage renal disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

nor health-related quality of life when comparing metformin monotherapy to Glucagon-like peptide 1 analogues in the treatment of type 2 diabetes.

Approved

* exenatide (brand names Byetta and Bydureon, manufactured by AstraZeneca), approved in 2005/2012 * liraglutide (Victoza for diabetes, Saxenda for obesity, manufactured by Novo Nordisk), approved in 2010 * lixisenatide (Lyxumia in Europe, Adlyxin in the United States, manufactured by Sanofi), approved in 2016 * albiglutide (Tanzeum, manufactured by GSK), approved in 2014 * dulaglutide (Trulicity, manufactured by Eli Lilly), approved in 2014 *

semaglutide Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and as anti-obesity medication for long-term weight management, developed by Novo Nordisk in 2012. S ...

(Ozempic and Rybelsus for diabetes, Wegovy for obesity, manufactured by Novo Nordisk), approved in 2017 *

tirzepatide Tirzepatide, sold under the brand name Mounjaro, is an antidiabetic medication used for the treatment of type 2 diabetes. Tirzepatide is given by weekly subcutaneous injection (under the skin). The most common side effects include nausea, vom ...

(Mounjaro, manufactured by Eli Lilly), approved in 2022

Under investigation

taspoglutide Taspoglutide is a former experimental drug, a glucagon-like peptide-1 agonist (GLP-1 agonist), that was under investigation for treatment of type 2 diabetes and being codeveloped by Ipsen and Roche. Initially, phase II trials reported it w ...

, phase III halted Sept 2010 *efpeglenatide

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.

References

{{Oral hypoglycemics and insulin analogs