EOS med chem works with you to know about Dulaglutide ↴
↠ Background:
Dulaglutide (doo" la gloo' tide) is a glucagon-like peptide-1 (GLP-1) analogue that acts like the native gastrointestinal hormone (incretin) to increase insulin secretion. Dulaglutide reproduces the activity of GLP-1, binding to specific receptors on pancreatic beta cells and increasing insulin secretion, which can lead to improvement of glycemic control in patients with type 2 diabetes. Dulaglutide, like other GLP-1 analogues, also causes weight loss which may contribute to its clinical effects. Dulaglutide is a recombinant DNA produced polypeptide that shares 97% homology to endogenous human GLP-1(7-37), but has an amino acid substitution which makes it resistant to DPP-4 degradation and thus extends its half-life in serum. In addition, the GLP-1 like polypeptide is linked to an Fc fragment of human IgG4 which further prolongs its serum half-life and duration of activity. Dulaglutide, like other GLP-1 analogues, must be given parenterally. Dulaglutide was approved for use in the United States in 2014 and current indications are for management of glycemic control in adults with type 2 diabetes in combination with diet and exercise, with or without other oral hypoglycemic agents. Dulaglutide is available under the brand name Trulicity in solution for subcutaneous injection in prefilled, single dose pens or syringes (0.75 and 1.5 mg/0.5 mL). The typical initial dose is 0.75 mg once weekly, which can be increased to 1.5 mg weekly. Dulaglutide is generally well tolerated, but side effects can be dose limiting and include nausea [~20%], vomiting [~5%], diarrhea [~12%], abdominal pain, decreased appetite, dyspepsia and fatigue. Rare side effects include pancreatitis [0.1-0.3%], hypoglycemia and hypersensitivity reactions.
↠ Introduction:
Dulaglutide is a recombinant DNA produced polypeptide analogue of human glucagon-like peptide-1 (GLP-1) which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other antidiabetic agents. There have been no published reports of hepatotoxicity attributed to dulaglutide therapy.
Name Dulaglutide
CAS: 923950-08-7
sequence:
His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp- Leu-Val-Lys-Gly-Gly-Gly
Purity: >98%
Molecular formula: C149H221N37O49
Molecular weight: 3314.62
Protein structure:
We have more than 50g in stock, assay 99% in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
↠ 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.[4][non-primary source needed]
As of 2017 it is unclear if they affect a person's risk of death.
↠ 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, 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.
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↠ References
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 ."FDA approves Trulicity to treat type 2 diabetes" (Press release). FDA. Sep 18, 2014.
4. 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. doi:10.1507/endocrj.ej14-0147. PMID 25029955. Retrieved 2014-09-29.[non-primary source needed]
5.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.
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. PMC 4113177 . PMID 24742660. Retrieved 2015-03-01.
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.
10. 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.
