Semaglutide compounding is being shut down– can a gummies hack keep it alive?

And will patients turn on Trump and RFK as hundreds of thousands lose access to GLP-1s?

Gummies to the rescue?

Over a million Americans (we don’t know exactly how many) have used online services to buy ‘compounded’ versions of popular GLP-1 weight loss drugs, like Ozempic (semaglutide) and Zepbound (tirzepatide). These services were allowed to manufacture and sell unbranded versions of these medicines, even though they are still under patent, due to shortages of the branded versions.

Eli Lilly’s Zepbound and Mounjaro have recently left shortage status and the FDA has announced that compounding tirzepatide must end by February 18 for 503A pharmacies (and March 19 for 503B pharmacies).

Today the FDA announced that Novo Nordisk’s Ozempic and Wegovy (semaglutide) are also no longer in shortage and that compounding will have to shut down in 60 to 90 days. This news has much bigger implications than shutting down tirzepatide compounding, because with tirzepatide already shutting down, there’s no fallback GLP-1 for people to switch over to.

Over the next few months there will be frantic stockpiling by patients. Meanwhile, compounders are fighting back, filing lawsuits against the FDA in an attempt to keep the door open. There’s also a workaround being attempted, that, as far as I know, hasn’t been reported on before: brand name Rybelsus compounded into gummies.

Here’s where it gets really sticky

The FDA is in a tough spot. Ending compounding makes sense legally and, for safety reasons, the FDA would prefer that people receive medications from approved drug makers. On the other hand, GLP-1 drugs are remarkably safe, there have been virtually no negative outcomes from the existing compounding, compounding manufacturers do follow regulations, and GLP-1s are broadly health-promoting. It’s clear that taking away GLP-1 access from people will generally worsen their health or drive them to riskier alternative peptide sources.

There’s four main reasons why people buy these drugs from online and other compounding services rather than getting them from their doctor and typical pharmacies:

1. It’s much cheaper if you can’t get insurance coverage: $200/month vs $1000/month. (And this is a good chance to remind everyone that these medications cost 400% more in the US than they do in other countries— if Ozempic was sold in the US for the same price that it’s sold in Canada, people would just buy the brand name drug at full price from Novo Nordisk.)

2. It’s easier and more private to get a GLP-1 prescribed through online services and have it delivered to your house.

3. It’s easier and more affordable to get access for off-label uses, including substance use disorders, modest weight loss (below obesity BMI levels), and hormone control.

4. Compounded GLP-1 comes in vials— dosing without an autoinjector is more flexible and allows for easier microdosing.

For millions of people, the compounding market is their only realistic path for weight loss and other positive health outcomes.

If you cut everyone off, patients will switch to unlicensed peptide vendors

While tirzepatide is considered a more effective drug for weight loss, the end of tirzepatide compounding was not earth shaking—patients switched to compounded semaglutide and still maintain most of the benefits. Taking away semaglutide as well, however, will truly cut people off from medicine that has transformed their lives.

If semaglutide compounding ends, patients will be in a panic. Eli Lilly and Novo Nordisk argue that their branded supply keeps people safe, but if licensed compounders shut down, people will flock to unregulated peptide suppliers outside the US. These services offer powdered semaglutide and tirzepatide, which patients mix with water to reconstitute, at prices that are even cheaper than compounders. (Amazingly, some patients have already been buying generic Cagrisema from peptide vendors before the branded version has even been approved.)

Lawsuits and a Superbowl Ad

In an attempt to fight back against a potential shut down, Hims ran this Superbowl ad, which was clearly targeted to influence policy and public opinion as much as to sell semaglutide:

There are also lawsuits in progress, seeking to delay or reverse the FDA’s compounding crackdowns.

A magical gummy workaround?

Existing semaglutide compounding services are looking for ways around a potential FDA ban on manufacturing semaglutide. Some are adding other ingredients like vitamin B-12 in an attempt to argue that this new formulation is essential for some patients and not available from the patent-holders. This may or may not hold much water in court.

But there is a hack that has a better chance at keeping semaglutide available indefinitely: gummies and lozenges.

Probably not the actual manufacturing process.

Traditionally, compounding pharmacies don’t manufacture drugs, but instead reformulate branded medications. For example, if a patient can’t swallow pills and there is no manufacturer-produced liquid version, a compounding pharmacy can grind up the pills and mix them into a syrup. Drug companies and the FDA allow this because the drugs are still being manufactured and sold through official channels. This is what you might call ‘normal compounding’.

As the FDA shuts down the shortage-based compounding, pharmacies will presumably only be able to source semaglutide from Novo Nordisk, at full price. But Novo does sell a less popular formulation of semaglutide that has a lot more of the active ingredient: Rybelsus.

Because semaglutide is a fragile peptide, it does not survive well in the stomach—that’s why Ozempic and Wegovy are injected. Rybelsus is a pill and it buffers the semaglutide with other ingredients that enable a very small percentage of it to survive the stomach and get into the blood (less than 1%). Rybelsus doesn’t work as well as Ozempic and has more gastrointestinal side effects, so it’s far less popular. Because Rybelsus is designed with the understanding that most of it will break down in the stomach, Novo puts a LOT of semaglutide into each pill. A weekly dose of Ozempic contains just 1mg or 2mg of semaglutide, whereas a week of Rybelsus pills contain 50mg or 100mg of semaglutide.

This creates an opening for compounders. If their ability to manufacture semaglutide is shut down by the FDA, they can continue buying Rybelsus and reformulating it— that’s more like “normal compounding”. But how can they get ground up Rybelsus into your body without all that breakdown in the stomach?

Gummies! Sucking on a gummy or a lozenge may provide much better absorption (sublingually) than you would get through your stomach, which means you would need much less in each gummy than you would need in each pill.

The math for these pharmacies works roughly like this:

• One month supply of high dose Rybelsus: $600-$1,000

• Semaglutide in Rybelsus: 14mg per pill x 30 pills = 420mg

• Semaglutide needed for a month of gummies: 1mg per gummy x 30 days = 30mg

• 420mg / 30mg = 14 months of gummies per box of Rybelsus = $71 of Rybelsus

As you can see, compounders can get enough semaglutide for a month of gummies from just two pills of Rybelsus. Even after paying full price for a box of Rybelsus and doing the work of reformulating the pills into gummies, pharmacies can end up with a product that’s affordable for their patients and profitable for them.

And this isn’t just hypothetical. We’ve spoken with two different compounding services that are planning to release sublingual lozenges or gummies with this strategy and there are several gummies already on the market, including from Eden and Strut and Henry Meds (oral drops in their case). Presumably the current oral offerings are made with bulk semaglutide for now but they may make this same switch to Rybelsus when semaglutide compounding is shut down.

How well do gummies actually work? How much semaglutide gets absorbed? No one really knows, or, at least, no studies have been published so far. The fact that several companies are selling them suggests that there is at least some efficacy— semaglutide is a medicine where the effects (weight loss, craving reduction) are fairly obvious to patients.

But there’s a legal gray area here– under FDA regulations, normal compounding is not supposed to allow formulations that are ‘essentially a copy’ of commercially available products unless there is a documented medical need for whatever the difference in the formulation is. Will compounders be able to make the case that gummies are medically necessary? They might argue that people who can’t swallow pills and are also needle-phobic can’t take Rybelsus or Ozempic. Expect more lawsuits.

The next FDA chief is a former semaglutide compounder: will he keep it alive?

Dr. Marty Makary, nominated to head the FDA under Trump, will be arriving to the position apparently aligned with the compounders. Until being nominated, he was listed as the Chief Medical Officer of telehealth company Sesame, which sells compounded semaglutide, and he’s on the board of Harrow, which does compounding in opthamology. When he comes into the role, he won’t be allowed to hold stock or equity in any company under FDA regulation, but presumably his existing roles indicate some support for compounding. He has some ammunition on the public health side— the initial safety concerns around compounding have not been borne out by the data and studies show that the mortality reductions from taking GLP-1s are strong.

Will he try to find a way to keep semaglutide compounding available? If not, the gummies will be ready and lawsuits will likely decide what happens next.