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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Mini-Review Article

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2

Author(s): Rami A. Al-Horani* and Milad Chedid

Volume 23, Issue 8, 2023

Published on: 22 February, 2023

Page: [1046 - 1050] Pages: 5

DOI: 10.2174/1871530322666221004151212

Price: $65

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Abstract

Tirzepatide (mounjaro®) is a derivative of the human glucose-dependent insulinotropic polypeptide (GIP) hormone with a position-20 being modified with 1,20- eicosanedioic acid via a chemical linker. It acts as a glucagon-like peptide-1 (GLP-1) receptor and GIP receptor agonist. It has recently been approved by FDA as an adjunct therapy to exercise and diet to improve glycemic control in patients with type II diabetes mellitus (T2DM). It represents a new transforming paradigm in the management of T2DM. This mini-review will shed light on its different pharmacokinetic and pharmacodynamic aspects.

Keywords: Tirzepatide, T2DM, GLP-1, GIP, Semaglutide, Dulaglutide.

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Graphical Abstract

[1]
King, M.W. Diabetes Mellitus. In: Integrative Medical Biochemistry Examination and Board Review; McGraw Hill: New York, 2014. Available from: https://accesspharmacy.mhmedical.com/content.aspx?bookid=1696&sectionid=111400703 (Accessed on: May 16, 2022).
[2]
Trujillo, J.; Haines, S. Diabetes Mellitus. In: Pharmacotherapy: A Pathophysiologic Approach, 11e; DiPiro, J.T.; Yee, G.C.; Posey, L.; Haines, S.T.; Nolin, T.D.; Ellingrod, V., Eds.; McGraw Hill: New York, 2020. Available from: https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577&sectionid=228901946 (Accessed on: May 16, 2022).
[3]
Powers, A.C.; Fowler, M.J.; Rickels, M.R. Diabetes Mellitus: Management and therapies. In: Harrison’s Principles of Internal Medicine 21e; Loscalzo, J.; Fauci, A.; Kasper, D.; Hauser, S.; Longo, D.; Jameson, J., Eds.; McGraw Hill: New York, 2022. Available from: https://accesspharmacy.mhmedical.com/content.aspx?bookid=3095&sectionid=265445871 (Accessed on: May 16, 2022).
[4]
Katzung, B.G.; Kruidering-Hall, M.; Tuan, R.; Vanderah, T.W.; Trevor, A. J Pancreatic Hormones, Antidiabetic Drugs, & Glucagon. Katzung. In: Katzung & Trevor’s Pharmacology: Examination & Board Review, 13e; McGraw Hill: New York, 2021.
[5]
Inaishi, J.; Saisho, Y. Exenatide once weekly for management of type 2 diabetes: A review. Clin. Pharmacol., 2022, 14, 19-26.
[http://dx.doi.org/10.2147/CPAA.S288846] [PMID: 35422660]
[6]
American Diabetes Association (ADA). Standards of medical care in diabetes-2021. Diabetes Care, 2021, 44(Suppl. 1), S1-S2.
[http://dx.doi.org/10.2337/dc21-Sint] [PMID: 33298409]
[7]
Bethel, M.A.; Mentz, R.J.; Merrill, P.; Buse, J.B.; Chan, J.C.; Goodman, S.G.; Iqbal, N.; Jakuboniene, N.; Katona, B.; Lokhnygina, Y.; Lopes, R.D.; Maggioni, A.P.; Ohman, P.; Tankova, T.; Bakris, G.L.; Hernandez, A.F.; Holman, R.R. Microvascular and cardiovascular outcomes according to renal function in patients treated with once-weekly exenatide: Insights from the exscel trial. Diabetes Care, 2020, 43(2), 446-452.
[http://dx.doi.org/10.2337/dc19-1065] [PMID: 31757838]
[8]
Blevins, T.; Pullman, J.; Malloy, J.; Yan, P.; Taylor, K.; Schulteis, C.; Trautmann, M.; Porter, L. Duration-5: Exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J. Clin. Endocrinol. Metab., 2011, 96(5), 1301-1310.
[http://dx.doi.org/10.1210/jc.2010-2081] [PMID: 21307137]
[9]
Davies, M.J.; D’Alessio, D.A.; Fradkin, J.; Kernan, W.N.; Mathieu, C.; Mingrone, G.; Rossing, P.; Tsapas, A.; Wexler, D.J.; Buse, J.B. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 2018, 41(12), 2669-2701.
[http://dx.doi.org/10.2337/dci18-0033] [PMID: 30291106]
[10]
DiMeglio, L.A.; Acerini, C.L.; Codner, E.; Craig, M.E.; Hofer, S.E.; Pillay, K.; Maahs, D.M. ISPAD clinical practice consensus guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr. Diabetes, 2018, 19(Suppl. 27), 105-114.
[http://dx.doi.org/10.1111/pedi.12737] [PMID: 30058221]
[11]
Guja, C.; Frías, J.P.; Suchower, L.; Hardy, E.; Marr, G.; Sjöström, C.D.; Jabbour, S.A. Safety and efficacy of exenatide once weekly in participants with type 2 diabetes and stage 2/3 chronic kidney disease. Diabetes Ther., 2020, 11(7), 1467-1480.
[http://dx.doi.org/10.1007/s13300-020-00815-z] [PMID: 32306296]
[12]
Hiles, R.A.; Bawdon, R.E.; Petrella, E.M. Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4). Hum. Exp. Toxicol., 2003, 22(12), 623-628.
[http://dx.doi.org/10.1191/0960327103ht402oa] [PMID: 14992323]
[13]
Holman, R.R.; Bethel, M.A.; Mentz, R.J.; Thompson, V.P.; Lokhnygina, Y.; Buse, J.B.; Chan, J.C.; Choi, J.; Gustavson, S.M.; Iqbal, N.; Maggioni, A.P.; Marso, S.P.; Öhman, P.; Pagidipati, N.J.; Poulter, N.; Ramachandran, A.; Zinman, B.; Hernandez, A.F. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med., 2017, 377(13), 1228-1239.
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[14]
LeRoith, D.; Biessels, G.J.; Braithwaite, S.S.; Casanueva, F.F.; Draznin, B.; Halter, J.B.; Hirsch, I.B.; McDonnell, M.E.; Molitch, M.E.; Murad, M.H.; Sinclair, A.J. Treatment of diabetes in older adults: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab., 2019, 104(5), 1520-1574.
[http://dx.doi.org/10.1210/jc.2019-00198] [PMID: 30903688]
[15]
Romera, I.; Cebrián, C.A.; Álvarez, G.F.; Gomez, P.F.; Reviriego, J. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes. Diabetes Ther., 2019, 10(1), 5-19.
[http://dx.doi.org/10.1007/s13300-018-0535-9] [PMID: 30506340]
[16]
Trujillo, J.M.; Goldman, J. Lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist for the treatment of adults with type 2 diabetes. Pharmacotherapy, 2017, 37(8), 927-943.
[http://dx.doi.org/10.1002/phar.1962] [PMID: 28556176]
[17]
Montanya, E.; Sesti, G. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin. Ther., 2009, 31(11), 2472-2488.
[http://dx.doi.org/10.1016/j.clinthera.2009.11.034] [PMID: 20109994]
[18]
Konwar, M.; Bose, D.; Jaiswal, S.K.; Maurya, M.; Ravi, R. Efficacy and safety of liraglutide 3.0 mg in patients with overweight and obese with or without diabetes: A systematic review and meta-analysis. Int. J. Clin. Pract., 2022, 2022, 1201977.
[http://dx.doi.org/10.1155/2022/1201977] [PMID: 35936066]
[19]
Apovian, C.M.; Aronne, L.J.; Bessesen, D.H.; McDonnell, M.E.; Murad, M.H.; Pagotto, U.; Ryan, D.H.; Still, C.D. Pharmacological management of obesity: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab., 2015, 100(2), 342-362.
[http://dx.doi.org/10.1210/jc.2014-3415] [PMID: 25590212]
[20]
Croom, K.F.; McCormack, P.L. Liraglutide. Drugs, 2009, 69(14), 1985-2004.
[http://dx.doi.org/10.2165/11201060-000000000-00000] [PMID: 19747013]
[21]
Danne, T.; Biester, T.; Kapitzke, K.; Jacobsen, S.H.; Jacobsen, L.V.; Petri, K.C.C.; Hale, P.M.; Kordonouri, O. Liraglutide in an adolescent population with obesity: A randomized, double-blind, placebo-controlled 5-week trial to assess safety, tolerability, and pharmacokinetics of liraglutide in adolescents aged 12-17 years. J. Pediatr., 2017, 181, 146-153.e3.
[http://dx.doi.org/10.1016/j.jpeds.2016.10.076] [PMID: 27979579]
[22]
Das, S.R.; Everett, B.M.; Birtcher, K.K.; Brown, J.M.; Cefalu, W.T.; Januzzi, J.L., Jr; Kalyani, R.R.; Kosiborod, M.; Magwire, M.L.; Morris, P.B.; Sperling, L.S. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease. J. Am. Coll. Cardiol., 2018, 72(24), 3200-3223.
[http://dx.doi.org/10.1016/j.jacc.2018.09.020] [PMID: 30497881]
[23]
Egan, A.G.; Blind, E.; Dunder, K.; De Graeff, P.A.; Hummer, B.T.; Bourcier, T.; Rosebraugh, C. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N. Engl. J. Med., 2014, 370(9), 794-797.
[http://dx.doi.org/10.1056/NEJMp1314078] [PMID: 24571751]
[24]
Hiramatsu, T.; Ozeki, A.; Asai, K.; Saka, M.; Hobo, A.; Furuta, S. Liraglutide improves glycemic and blood pressure control and ameliorates progression of left ventricular hypertrophy in patients with type 2 diabetes mellitus on peritoneal dialysis. Ther. Apher. Dial., 2015, 19(6), 598-605.
[http://dx.doi.org/10.1111/1744-9987.12319] [PMID: 26556397]
[25]
Htike, Z.Z.; Zaccardi, F.; Papamargaritis, D.; Webb, D.R.; Khunti, K.; Davies, M.J. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes. Metab., 2017, 19(4), 524-536.
[http://dx.doi.org/10.1111/dom.12849] [PMID: 27981757]
[26]
Idorn, T.; Knop, F.K.; Jørgensen, M.B.; Jensen, T.; Resuli, M.; Hansen, P.M.; Christensen, K.B.; Holst, J.J.; Hornum, M.; Feldt, R.B. Safety and efficacy of liraglutide in patients with type 2 diabetes and end-stage renal disease: An investigator-initiated, placebo-controlled, double-blind, parallel-group, randomized trial. Diabetes Care, 2016, 39(2), 206-213.
[http://dx.doi.org/10.2337/dc15-1025] [PMID: 26283739]
[27]
Jacobsen, L.V.; Hindsberger, C.; Robson, R.; Zdravkovic, M. Effect of renal impairment on the pharmacokinetics of the GLP-1 analogue liraglutide. Br. J. Clin. Pharmacol., 2009, 68(6), 898-905.
[http://dx.doi.org/10.1111/j.1365-2125.2009.03536.x] [PMID: 20002084]
[28]
Tamborlane, W.V.; Barrientos, P.M.; Fainberg, U.; Frimer, L.H.; Hafez, M.; Hale, P.M.; Jalaludin, M.Y.; Kovarenko, M.; Libman, I.; Lynch, J.L.; Rao, P.; Shehadeh, N.; Turan, S.; Weghuber, D.; Barrett, T. Liraglutide in children and adolescents with type 2 diabetes. N. Engl. J. Med., 2019, 381(7), 637-646.
[http://dx.doi.org/10.1056/NEJMoa1903822] [PMID: 31034184]
[29]
Srivastava, G.; Fox, C.K.; Kelly, A.S.; Jastreboff, A.M.; Browne, A.F.; Browne, N.T.; Pratt, J.S.A.; Bolling, C.; Michalsky, M.P.; Cook, S.; Lenders, C.M.; Apovian, C.M. Clinical considerations regarding the use of obesity pharmacotherapy in adolescents with obesity. Obesity (Silver Spring), 2019, 27(2), 190-204.
[http://dx.doi.org/10.1002/oby.22385] [PMID: 30677262]
[30]
Scott, L.J. Dulaglutide: A review in type 2 diabetes. Drugs, 2020, 80(2), 197-208.
[http://dx.doi.org/10.1007/s40265-020-01260-9] [PMID: 32002850]
[31]
Aroda, V.R.; Blonde, L.; Pratley, R.E. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev. Endocr. Metab. Disord., 2022, 23, 979-994.
[http://dx.doi.org/10.1007/s11154-022-09735-8] [PMID: 35838946]
[32]
Singh, G.; Krauthamer, M.; Bjalme, E.M. Wegovy (semaglutide): A new weight loss drug for chronic weight management. J. Investig. Med., 2022, 70(1), 5-13.
[http://dx.doi.org/10.1136/jim-2021-001952] [PMID: 34706925]
[33]
Syed, Y.Y. Tirzepatide: First approval. Drugs, 2022, 82(11), 1213-1220.
[http://dx.doi.org/10.1007/s40265-022-01746-8] [PMID: 35830001]
[34]
Bokvist, B.K.; Coskun, T.; Cummins, R.C.; Alsina, F.J. GIP and GLP-1 co-agonist compounds. U.S. Patent 9474780, 2016.
[35]
Frederick, M.O.; Boyse, R.A.; Braden, T.M.; Calvin, J.R.; Campbell, B.M.; Changi, S.M.; Coffin, S.R.; Condon, C.; Gowran, O.; McClary Groh, J.; Groskreutz, S.R.; Harms, Z.D.; Humenik, A.A.; Kallman, N.J.; Klitzing, N.D.; Kopach, M.E.; Kretsinger, J.K.; Lambertus, G.R.; Lampert, J.T.; Maguire, L.M.; Moynihan, H.A.; Mullane, N.S.; Murphy, J.D.; O’Mahony, M.E.; Richey, R.N.; Seibert, K.D.; Spencer, R.D.; Strege, M.A.; Tandogan, N.; Torres, T.F.L.; Tsukanov, S.V.; Xia, H. Kilogram-scale GMP manufacture of tirzepatide using a hybrid SPPS/LPPS approach with continuous manufacturing. Org. Process Res. Dev., 2021, 25(7), 1628-1636.
[http://dx.doi.org/10.1021/acs.oprd.1c00108]
[36]
Min, T.; Bain, S.C. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: The surpass clinical trials. Diabetes Ther., 2021, 12(1), 143-157.
[http://dx.doi.org/10.1007/s13300-020-00981-0] [PMID: 33325008]
[37]
Pucino, F. Center for drug evaluation and research. New drug application: 215866 (Tirzepatide). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215866Orig1s000MedR. pdf (Accessed on: Aug 26, 2022).

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