Spotlight on a New Peptide Approval, Tirzepatide

First published: May 25, 2022

As our focus at AmbioPharm is on peptides, it is always exciting to see a new peptide drug approval.  Recently, Eli Lilly received an approval by the FDA for tirzepatide (Mounjaro™) for the treatment of adults with type II diabetes (T2D).

Type II diabetes is a condition where the body produces insulin at insufficient levels.  Incretin hormones, or gut peptides, play a role in insulin secretion called the incretin effect.   Of these incretins, glucose-dependent insulinotropic polypeptide (GIP) is found in the upper gut, while glucagon-like peptide 1 (GLP-1) is found in the lower gut.  Several glucagon-like peptide 1 (GLP-1) receptor agonists, or GLP-1Ras, have already been developed and approved for the treatment of type-2 diabetes (such as exenatide, lixisenatide, liraglutide, and semaglutide) via subcutaneous injection. An agonist binds to a receptor protein triggering a biological response and these receptor agonists function by stimulating the production of insulin in the patient following administration.  Meanwhile, incretins are metabolized by dipeptidyl peptidase 4 (DPP-4) and overcoming DPP-4 degradation can be a challenge that scientists have had to overcome. Another strategy in avoiding degradation is adding a DPP-4 inhibitor alongside a GLP-1RA.¹

What makes tirzepatide unique is that it is one molecule that is both a GIP and a GLP-1 receptor agonist, or a dual agonist.² 

Update (Oct 6, 2022): Eli Lilly receives U.S. FDA Fast Track designation for tirzepatide for the treatment of adults with obesity and plans a rolling submission of a new drug application (NDA). It is currently in Phase III clinical trials for this indication.³

References:

1. Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018 Feb; 20 Suppl 1:5-21. doi: 10.1111/dom.13129. PMID: 29364588. Retrieved May 2022: https://pubmed.ncbi.nlm.nih.gov/29364588/
2. FDA approves Lilly’s Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjarotm-tirzepatide-injection-first-and
3. Lilly receives U.S. FDA Fast Track designation for tirzepatide for the treatment of adults with obesity, or overweight with weight-related comorbidities. https://investor.lilly.com/news-releases/news-release-details/lilly-receives-us-fda-fast-track-designation-tirzepatide

Further reading:

• Blog: 100 Years of Insulin: A Triumph of Science
• Blog: Oral Semaglutide Approved by FDA
• Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. PMID: 31031702; PMCID: PMC6474072. https://pubmed.ncbi.nlm.nih.gov/31031702/
• Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, Bekiari E. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022 May 17:1–11. doi: 10.1007/s00125-022-05715-4. Epub ahead of print. PMID: 35579691; PMCID: PMC9112245. https://pubmed.ncbi.nlm.nih.gov/35579691/
• Thomas MK, Nikooienejad A, Bray R, et al. Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021;106(2):388-396. doi:10.1210/clinem/dgaa863 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823251/