Glucagon-like peptide-1 receptor agonist

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. 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

Under investigation

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]

References
  1. Baggio LL (2008). "Glucagon-like Peptide-1 Analogs Other Than Exenatide". Medscape Diabetes & Endocrinology.
  2. Ali ES, Hua J, Wilson CH, Tallis GA, Zhou FH, Rychkov GY, Barritt GJ (2016). "The glucagon-like peptide-1 analogue exendin-4 reverses impaired intracellular Ca2+ signalling in steatotic hepatocytes". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1863 (9): 2135–46. doi:10.1016/j.bbamcr.2016.05.006. PMID 27178543.
  3. American Diabetes Association (2012). "Standards of medical care in diabetes—2012". Diabetes Care. 35 Suppl 1: S11–63. doi:10.2337/dc12-s011. PMC 3632172. PMID 22187469.
  4. Das, Anju; Geetha, K. M.; Hazarika, Iswar (29 August 2019). "Contemporary Updates on the Physiology of Glucagon like Peptide-1 and Its Agonist to Treat Type 2 Diabetes Mellitus". International Journal of Peptide Research and Therapeutics. doi:10.1007/s10989-019-09927-y.
  5. Forsmark, CE (2016). "Incretins, Diabetes, Pancreatitis and Pancreatic Cancer: What the GI specialist needs to know". Pancreatology. 16 (1): 10–3. doi:10.1016/j.pan.2015.11.009. PMID 26795258.
  6. Schroeder, C. "Incretin Meds Like Januvia and Victoza Again Linked to Pancreatic Cancer". DrugNews. Retrieved 24 February 2018.
  7. Liu, J; Li, L; Deng, K; Xu, C; Busse, JW; Vandvik, PO; Li, S; Guyatt, GH; Sun, X (8 June 2017). "Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis". BMJ (Clinical Research Ed.). 357: j2499. doi:10.1136/bmj.j2499. PMC 5463186. PMID 28596247.
  8. Zheng, Sean L.; Roddick, Alistair J.; Aghar-Jaffar, Rochan; Shun-Shin, Matthew J.; Francis, Darrel; Oliver, Nick; Meeran, Karim (2018-04-17). "Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes". JAMA. 319 (15): 1580–1591. doi:10.1001/jama.2018.3024. hdl:10044/1/60316. ISSN 0098-7484. PMC 5933330. PMID 29677303.
  9. "FDA Approves New Treatment for Type 2 Diabetes".
  10. "FDA approves Adlyxin to treat type 2 diabetes". 2019-09-10.
  11. "FDA Approves Weekly Injectable Diabetes Drug: Albiglutide".
  12. "FDA Approves Weekly Injectable Diabetes Drug: Dulaglutide".
  13. Longer Acting GLP-1 Receptor Agonists and the Potential for Improved Cardiovascular Outcomes. 2013
  14. "GLP-1 Receptor Agonists vs. DPP-4 Inhibitors for Type 2 Diabetes".


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