Semaglutide offers a transformative approach to treating type 2 diabetes by improving glycemic control, reducing cardiovascular risks, and promoting weight loss. With its favorable safety profile and potential for improved patient outcomes, Semaglutide has tremendous value in the field of diabetes therapeutics. Seamlessly incorporate our intermediates into your manufacturing process, ensuring a steady supply of this exceptional medication. Join us in advancing diabetes management and improving patient health. Embrace Semaglutide and contribute to a healthier, more productive future.

Semaglutide, a peptide drug, compared to traditional small molecule drugs, has the following disadvantages:

- Injection is a common route of administration for peptide drugs. The invasive nature lowers the patient compliance. 

- Most peptides and protein drugs have short circulation time and thus short half-lives. They are prone to intracellular and extracellular degradation, and renal elimination. 

- Higher immunogenicity due to large sizes.

- Low permeability.

Apart from utilization of absorption enhancer such as SNAC, another way to address these challenges is through covalent modification; and this product, a C18 fatty acid, octadecanedioic acid, is a success of such strategy.

Lipidation of peptide and proteins

The process of lipidation in peptide drugs refers to coupling a fatty chain to an appropriate group in the peptide molecule. In nature, cells use lipidation to control the function and intracellular localization of certain proteins. When this modification technique is applied to, in this case, Semaglutide, it can significantly enhance the half-life and cell permeability of the peptide. This modification significantly increases the half-life from 1~1.5 hours to 168 hours, mainly through the enhanced hydrophobicity and the interaction with albumin. In addition, it enables the oral route of Semaglutide, marketed as Rybelsus since 2019 by FDA.

Semaglutide structure and lipidation with octadecanedioic acid.

Even though the more common polyethylene glycol (PEG) modification may also achieve these effects, some studies show that under certain circumstances, the advantages of lipidation modification surpass those of PEG. Some lipid-modified peptide drugs have already been approved by the FDA. For example, Tirzepatide (Mounjaro), a type 2 diabetes injection drug released by Eli Lilly in 2022, is also a peptide drug conjugated to a C20 fatty diacid. The designers of drug molecules have added a very complex fat modification structure to the Tirzepatide molecule. The potential advantages of lipidation are mainly attributed to several key factors, such as enhancing the half-life, enhancing drug delivery, changing the route of administration, improving medicinal potency, and reducing immunogenicity.

Tirzepatide structure and lipidation with a C20 fatty acid.

References

K. Bellmann-Sickert, et al. Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation. J. Med. Chem., 2011, 54, 2658-2667.

L. Jensen, et al. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur. J. Pharm. Sci., 2017, 104, 31-41.