Glucagon-like peptide-1 receptor agonist

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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 detection of occult pancreatic cancer over non-insulin anti diabetic drugs (NIADs).[6][7]

Health effects[]

As of 2017 it was unclear if they affect a person's risk of death.[8] 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.[9]

Approved[]

  • exenatide (Byetta, Bydureon), approved in 2005/2012
  • liraglutide (Victoza, Saxenda), approved 2010[10]
  • lixisenatide (Lyxumia in Europe, Adlyxin in the United States), approved in 2016[11]
  • albiglutide (Tanzeum), approved in 2014 by GSK[12]
  • dulaglutide (Trulicity), approved in 2014—manufactured by Eli Lilly[13]
  • semaglutide (Ozempic, Rybelsus), approved in 2017.[14]

Under investigation[]

  • taspoglutide, phase III halted Sept 2010[1]
  • efpeglenatide[15]
  • tirzepatide[16]

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.[17]

References[]

  1. ^ Jump up to: a b 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. ^ https://care.diabetesjournals.org/content/41/2/286
  7. ^ Schroeder, C. "Incretin Meds Like Januvia and Victoza Again Linked to Pancreatic Cancer". DrugNews. Retrieved 24 February 2018.
  8. ^ 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.
  9. ^ 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.
  10. ^ "FDA Approves New Treatment for Type 2 Diabetes".
  11. ^ "FDA approves Adlyxin to treat type 2 diabetes". 2019-09-10.
  12. ^ "FDA Approves Weekly Injectable Diabetes Drug: Albiglutide".
  13. ^ "FDA Approves Weekly Injectable Diabetes Drug: Dulaglutide".
  14. ^ Longer Acting GLP-1 Receptor Agonists and the Potential for Improved Cardiovascular Outcomes. 2013
  15. ^ Gerstein, Hertzel C.; Sattar, Naveed; Rosenstock, Julio; Ramasundarahettige, Chinthanie; Pratley, Richard; Lopes, Renato D.; Lam, Carolyn S.P.; Khurmi, Nardev S.; Heenan, Laura; Del Prato, Stefano; Dyal, Leanne; Branch, Kelley (2021). "Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes". New England Journal of Medicine. doi:10.1056/NEJMoa2108269.
  16. ^ Frías, Juan P.; Davies, Melanie J.; Rosenstock, Julio; Pérez Manghi, Federico C.; Fernández Landó, Laura; Bergman, Brandon K.; Liu, Bing; Cui, Xuewei; Brown, Katelyn; SURPASS-2 Investigators (2021). "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes". New England Journal of Medicine. doi:10.1056/NEJMoa2107519. PMID 34170647.
  17. ^ "GLP-1 Receptor Agonists vs. DPP-4 Inhibitors for Type 2 Diabetes".


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