Dulaglutide

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Dulaglutide
Clinical data
Trade names Trulicity
AHFS/Drugs.com trulicity
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Injection
ATC code
Legal status
Legal status
Identifiers
CAS Number
IUPHAR/BPS
ChemSpider
  • none
KEGG
Chemical and physical data
Formula C2646H4044N704O836S18
Molar mass 59669.81 g/mol

Dulaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 agonist) consisting of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4. It is used 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 binds to glucagon-like peptide 1 receptors, slowing gastric emptying and increases insulin secretion by pancreatic Beta cells. Simultaneously the compound reduces the elevated glucagon secretion by inhibiting 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 because these problems are the result of the islet cells being unable to produce insulin and one of the actions of Dulaglutide is to stimulate functioning islet cell to produce more insulin. 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][non-primary source needed]

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" (Press release). 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. PMC 4159612Freely accessible. PMID 24373234. doi:10.1016/B978-0-12-800101-1.00002-8. 
  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. 61: 949–59. PMID 25029955. doi:10.1507/endocrj.ej14-0147. Retrieved 2014-09-29. [non-primary source needed]
  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. PMC 4113177Freely accessible. PMID 24742660. doi:10.2337/dc13-2761. Retrieved 2015-03-01. 
  7. ^ Amblee A (April 2014). "Dulaglutide for the treatment of type 2 diabetes". Drugs Today. 50 (4): 277–89. PMID 24918645. doi:10.1358/dot.2014.50.4.2132740. 
  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. PMID 24485345. doi:10.1016/j.diabres.2014.01.010. 
  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. PMID 23403741. doi:10.1097/MED.0b013e32835edb32. Retrieved 2014-09-30.