Scientists Think This Enzyme Could Dramatically Enhance Ozempic's Results

Ozempic (semaglutide) belongs to a class of diabetes drugs known as glucagon-like peptide-1 receptor agonists. Although Ozempic was originally developed to treat type 2 diabetes, it only became widely known when celebrities started using it for weight loss, with dramatic effects in some cases. It is now thought of as one of the best peptides for improving the body.

Currently, Ozempic is administered as a weekly injection or taken orally as a daily pill, but peptides in general are notoriously unstable in the body due to breakdown by enzymes called peptidases — though in the case of Ozempic, that could be countered by another enzyme called PapB. To measure that effect, scientists refer to something called the half-life when assessing the stability of a drug. The half-life is the time required for the concentration of a drug in the body to decrease by 50%. Compared to most peptides, Ozempic already has a long half-life of approximately 7 days, which enables it to be taken once a week.

Although a half-life of a week may sound pretty good, researchers at the University of Utah have now found that PapB that can modify Ozempic into a peptide ring (also called a cyclic peptide), which is more stable than a linear peptide structure — this may further prolong the half-life of Ozempic. It isn't a big leap to envision the development of a new drug in the future (call it "Ozempic 2.0") that could be injected less frequently, as the ring version of Ozempic has the potential for better binding to the GLP-1 receptor than the linear version. Therefore, PapB may enhance the effects of Ozempic, such as slowing of stomach emptying and stabilization of glucose levels.

The PapB enzyme is one of a group of enzymes called S-adenosyl-L-methionine RiPP maturases. According to the paper published by the University of Utah researchers in ACS Bio & Med Chem Au, an interesting feature of PapB is that it can tolerate a fair amount of variation in the site that it binds to on the peptide. However, just like other modifying enzymes, PapB does require some modification of the Ozempic sequence in order for the enzyme to work.

The idea is that the ring version of Ozempic may present a more bulky structure, which makes it harder for protease enzymes to access the part of Ozempic that's susceptible to attack. In theory, this should make the ring version more stable and prolong its half-life in the body. Another theory is that the ring structure would make Ozempic more rigid, which may help it to bind better to its receptor and bring about its effects.

The ring version of Ozempic, formed with the help of PapB, is still being researched and isn't approved by the FDA for use in humans. If it were to become available online, scientists warn that people should think twice before injecting it, or any other research peptides.  

In other words, the results are considered "proof-of-concept," which means that, although they may show promise, a lot more research needs to be done before we can confidently say that the ring version of Ozempic is better than the linear version in approved GLP-1 drugs. For example, the ring version of Ozempic will need to be studied in animals and humans to see if it still showcases better stability and efficacy in practice. On another note, if it's one day approved by the FDA, the ring version would have to be called by a new name — it can't be sold as "Ozempic" since it has a different sequence and structure.

The modification of peptides using PapB could open up a new avenue for taking existing peptide drugs and enhancing them to improve stability and efficacy. After all, more GLP-1 receptor agonist treatments keep coming on the market, including a new FDA-approved GLP-1 pill Foundayo, as well as the upcoming retatrutide, which has already been showing much greater weight loss effects than other GLP-1 agonists.