From day one of Novo Nordisk launching Wegovy (semaglutide) tablets, we have seen a sharp contrast. Experts have been standing back with a collective yawn, while real world experiences seem to favor these oral obesity meds.

“I haven’t prescribed them once,” confided a friend who is a nationally recognized expert in obesity medicine. That caution, as we have reported, is something we take seriously.

But a very different perspective continues to roll in from the real world as prescriptions fly out of U.S. pharmacies at a rate that makes this “the fastest drug launch ever” – 50,000 per week at the end of January.

Data and Anecdotes

Consistent with these data are anecdotal reports from people in clinical obesity care who are actually using Wegovy tablets. Earlier this week, obesity medicine physician Michael Albert wrote on social media:

“Early returns on Wegovy pill are positive. It appears better tolerated than Rybelsus and more effective at comparable doses.

“This represents our direct experience with patients. We have a rather large practice too. Hopefully we can present some of this data later this year or early next. One of our NPs is looking at real-world outcomes of oral sema in surgical and non-surgical populations.”

Indeed, we need more data. Anecdotes, even from smart clinicians, can present divergent ideas about real world experiences.

Apples, Oranges, and a Stealth Reformulation

Adding to the confusion about the potential value of Wegovy tablets in obesity is a stealthy reformulation of oral semaglutide.

Originally launched in doses ranging from 3 – 14 mg as Rybelsus, many clinicians are basing their beliefs about oral semaglutide on their very mixed experiences with this formulation.

However, without really saying much about it, Novo Nordisk appears to have refined their formulation of oral semaglutide for the launch of Wegovy tablets. An obvious difference is the dosage, which ranges up to 25 mg. But more important is the fact that the formulation used for Wegovy tablets has better bioavailability than the formulation of Rybelsus tablets. For Wegovy tablets, it’s 1 – 2%. The number for Rybelsus is 0.4 – 1%. Taken literally, that represents a doubling of the amount that enters circulation from a given dose of the new formulation.

Incidentally, a new formulation of oral semaglutide is coming to replace Rybelsus, launching as Ozempic tablets for type 2 diabetes.

New and Improved?

It is surprising that Novo Nordisk has been relatively quiet about this reformulation. One has to dig through arcane information in prescribing leaflets to find it. It appears that the OASIS 1 study of oral semaglutide for obesity at a dose of 50 mg was done with the old formulation.

The OASIS 4 study was done with a dose of 25 mg, presumably with the more advanced formulation. But nowhere in the publication of this study at the new, lower doses is this explained or discussed. They only mention that an earlier study was done at a higher dose. There’s no mention of differences in the drug used in these two different studies.

“New and improved” is a proven catch phrase for marketing. So it’s odd that Novo Nordisk makes little mention of the improvements the company has made to the formulation of oral semaglutide in comparison to Rybelsus.

This is a fact clinicians should know quite clearly.

Click here for the OASIS 4 study, here and here for more on the positive experiences with Wegovy tablets in the marketplace.

Through the Looking Glass, Humpty Dumpty, illustration by Peter Newell / Wikimedia Commons