Dulaglutide

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Dulaglutide
Clinical data
Legal status
  • Investigational
Identifiers
CAS number 923950-08-7
ATC code None
Chemical data
Formula C2646H4044N704O836S18 
Mol. mass 59669.81 g/mol

Dulaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 agonist) for the treatment of type 2 diabetes that can be used once weekly.[1][2]GLP-1 is a hormone that is involved in the normalization of level of glucose in blood (glycemia). The FDA approved dulaglutide for use in the United States in September 2014.[3] The drug is manufactured by Eli Lilly under the brand name Trulicity.[3]

Mechanism of action[edit]

Dulaglutide binding to glucagon-like peptide 1 receptor, slows gastric emptying and increases insulin secretion by beta cells in the pancreas. Simultaneously the compound reduces the elevated glucagon secretion by alpha cells of the pancreas, which is known to be inappropriate in the diabetic patient. GLP-1 is normally secreted by L cells of the gastrointestinal mucosa in response to a meal.[4]

Medical uses[edit]

The compound is indicated for adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control. Dulaglutide is not indicated in the treatment of subjects with type 1 diabetes mellitus or patients with diabetic ketoacidosis. Dulaglutide can be used either stand-alone or in combination with other medicines for type 2 diabetes, in particular metformin, sulfonylureas, thiazolidinediones, and insulin taken concomitantly with meals.[5]

Side effects[edit]

The most common side effects include gastrointestinal disorders, such as dyspepsia, decreased appetite, nausea, vomiting, abdominal pain, diarrhea.[6] Some patients may experience serious adverse reactions: acute pancreatitis (symptoms include persistent severe abdominal pain, sometimes radiating to the back and accompanied by vomiting), hypoglycemia, renal impairment (which may sometimes require hemodialysis). The risk of hypoglycemia is increased if the drug is used in combination with sulfonylureas or insulin.[7][8]

Contraindications[edit]

The compound is contraindicated in subjects with hypersensitivity to active principle or any of the product's components. As a precautionary measure patients with a personal or family history of medullary thyroid carcinoma or affected by multiple endocrine neoplasia syndrome type 2 should not take dulaglutide, because for now it is unclear whether the compound can increase the risk of these cancers.[9]

References[edit]

  1. ^ Courtney Aavang Tibble, Tricia Santos Cavaiola, Robert R Henry (2013). "Longer Acting GLP-1 Receptor Agonists and the Potential for Improved Cardiovascular Outcomes: A Review of Current Literature". Expert Rev Endocrinol Metab 8 (3): 247–259. doi:10.1586/eem.13.20. 
  2. ^ "Lilly's Once-Weekly Dulaglutide Shows Non-Inferiority to Liraglutide in Head-to-Head Phase III Trial for Type 2 Diabetes". Eli Lilly. Feb 25, 2014. 
  3. ^ a b "FDA approves Trulicity to treat type 2 diabetes" (Press release). FDA. Sep 18, 2014. 
  4. ^ Nadkarni P, Chepurny OG, Holz GG (2014). "Regulation of glucose homeostasis by GLP-1". Prog Mol Biol Transl Sci 121: 23–65. doi:10.1016/B978-0-12-800101-1.00002-8. PMC 4159612. PMID 24373234. Retrieved 2014-09-29. 
  5. ^ Terauchi Y, Satoi Y, Takeuchi M, Imaoka T (July 2014). "Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study". Endocr. J. PMID 25029955. Retrieved 2014-09-29. 
  6. ^ Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z (August 2014). "Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5)". Diabetes Care 37 (8): 2149–58. doi:10.2337/dc13-2761. PMID 24742660. 
  7. ^ Amblee A (April 2014). "Dulaglutide for the treatment of type 2 diabetes". Drugs Today 50 (4): 277–89. doi:10.1358/dot.2014.50.4.2132740. PMID 24918645. 
  8. ^ Monami M, Dicembrini I, Nardini C, Fiordelli I, Mannucci E (February 2014). "Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials". Diabetes Res. Clin. Pract. 103 (2): 269–75. doi:10.1016/j.diabres.2014.01.010. PMID 24485345. 
  9. ^ Samson SL, Garber A (April 2013). "GLP-1R agonist therapy for diabetes: benefits and potential risks". Curr Opin Endocrinol Diabetes Obes 20 (2): 87–97. doi:10.1097/MED.0b013e32835edb32. PMID 23403741. Retrieved 2014-09-30.