Dulaglutide

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Dulaglutide
Names
Trade namesTrulicity, others[1]
Clinical data
Drug classGLP-1 agonist[2]
Main usesType 2 diabetes[2]
Side effectsNausea, diarrhea, vomiting, abdominal pain, decreased appetite[3]
Pregnancy
category
Routes of
use
Subcutaneous
Typical dose0.75 to 4.5 mg q wk[3]
External links
AHFS/Drugs.comMonograph
US NLMDulaglutide
MedlinePlusa614047
Legal
License data
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Chemical and physical data
FormulaC2646H4044N704O836S18
Molar mass59670.63 g·mol−1

Dulaglutide, sold under the brand name Trulicity among others, is a medication used to treat type 2 diabetes.[3] Among those in this group at high risk, it may decrease the risk of heart disease.[3] It is used together with diet and exercise.[3] It is give once weekly by injection under the skin.[3]

Common side effects include nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.[3] Other side effects may include pancreatitis, low blood sugar, allergic reactions, kidney problems, and certain thyroid tumors.[3] It is a glucagon-like peptide-1 receptor agonist (GLP-1 agonist) which increases the amount of insulin released by the pancreas in response to food.[2]

Dulaglutide was approved for medical use in the United States and Europe in 2014.[3][2] In the United Kingdom it costs the NHS about £73 every 4 weeks at a dose of 1.5 mg.[5] This amount in the United States costs about 735 USD.[6] In 2018, it was the 149th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[7][8]

Medical uses

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.[9][non-primary source needed]

A 2017 meta-analysis did not support the suggestion that treatment with GLP-1 agonists or DPP-4 inhibitors increased all-cause mortality in type 2 diabetics.[10]

Dosage

It is started at a dose of 0.75 mg once per week and may be increased 4.5 mg once per week.[3]

Side effects

The most common side effects include gastrointestinal disorders, such as dyspepsia, decreased appetite, nausea, vomiting, abdominal pain, diarrhea.[11] 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.[12][13] There is also a potential risk of medullary thyroid carcinoma associated with the use of the drug.[14]

Contraindications

The compound is contraindicated in subjects with hypersensitivity to the active ingredient or any of the product's components.

People with a personal or family history of medullary thyroid cancer (MTC) or affected by multiple endocrine neoplasia type 2 should not take dulaglutide, because it could increase the risk of these cancers.[15][16]

Mechanism of action

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, as glucagon is known to be inappropriately elevated in diabetic patients. GLP-1 is normally secreted by L cells of the gastrointestinal mucosa in response to a meal.[17]

History

The safety and effectiveness of dulaglutide were evaluated in six clinical trials in which 3,342 subjects with type 2 diabetes received dulaglutide. Subjects receiving dulaglutide had an improvement in their blood sugar control as observed with reductions in HbA1c level (hemoglobin A1c is a measure of blood sugar control).[16]

The U.S. Food and Drug Administration (FDA) approved dulaglutide with a Risk Evaluation and Mitigation Strategy (REMS),[16] and granted the approval of Trulicity to Eli Lilly and Company.[16] The REMS consists of a number of steps that Eli Lilly will take to make physicians aware of the risk of pancreatitis and the potential risk of medullary thyroid carcinoma associated with the drug.[14]

Society and culture

Cost

In 2018, it was the 149th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[7][8]

References

  1. "Dulaglutide international". Drugs.com. 3 January 2020. Archived from the original on 5 February 2020. Retrieved 4 February 2020.
  2. 2.0 2.1 2.2 2.3 "Trulicity EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 23 February 2020. Retrieved 23 February 2020.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 "DailyMed - TRULICITY- dulaglutide injection, solution". dailymed.nlm.nih.gov. Archived from the original on 11 January 2022. Retrieved 27 December 2021.
  4. "Dulaglutide (Trulicity) Use During Pregnancy". Drugs.com. 15 July 2019. Archived from the original on 5 February 2020. Retrieved 4 February 2020.
  5. BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 738. ISBN 978-0857114105.
  6. "Dulaglutide Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 9 November 2016. Retrieved 27 December 2021.
  7. 7.0 7.1 "The Top 300 of 2021". ClinCalc. Archived from the original on 12 February 2021. Retrieved 18 February 2021.
  8. 8.0 8.1 "Dulaglutide – Drug Usage Statistics". ClinCalc. Archived from the original on 3 March 2021. Retrieved 18 February 2021.
  9. Terauchi Y, Satoi Y, Takeuchi M, et al. (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 (10): 949–59. doi:10.1507/endocrj.ej14-0147. PMID 25029955.[non-primary source needed]
  10. Liu J, Li L, Deng K, et al. (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.
  11. Nauck M, Weinstock RS, Umpierrez GE, et al. (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. PMC 4113177. PMID 24742660. Archived from the original on 28 March 2015. Retrieved 1 March 2015.
  12. 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.
  13. Monami M, Dicembrini I, Nardini C, et al. (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.
  14. 14.0 14.1 "Risk Evaluation and Mitigation Strategy (REMS)". United States Food and Drug Administration. September 2014. Archived from the original on 5 March 2021. Retrieved 24 March 2020.
  15. 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. S2CID 6933973.
  16. 16.0 16.1 16.2 16.3 "FDA approves Trulicity to treat type 2 diabetes" (Press release). U.S. Food and Drug Administration (FDA). 18 September 2014. Archived from the original on 20 April 2016. Retrieved 4 February 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  17. Nadkarni P, Chepurny OG, Holz GG (2014). "Regulation of glucose homeostasis by GLP-1". Glucose Homeostatis and the Pathogenesis of Diabetes Mellitus. Prog Mol Biol Transl Sci. Progress in Molecular Biology and Translational Science. Vol. 121. pp. 23–65. doi:10.1016/B978-0-12-800101-1.00002-8. ISBN 9780128001011. PMC 4159612. PMID 24373234.

Further reading

External links

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