Separating Compounded Semiglutide Myths from Truths

Peter J. Pitts, President of the Center for Medicine in the Public Interest

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The semaglutide shortage is over, but the illegal, unsafe, and venal exploitation of the American public by drug compounders masquerading as pharmaceutical companies continues. Let’s look at the facts.

Recently the FDA reclassified the semaglutide shortage as “resolved.” That means compounding of semaglutide will no longer be permitted under current regulations. The FDA said it will give compounding pharmacies time to wind down “to avoid unnecessary disruption to patient treatment.”

Over and done with? Hardly. The result of this largesse of regulatory discretion -- lawsuits from two shady outfits, the Outsourcing Facilities Association (OFA) and FarmaKeio Superior Custom Compounding alleging that the agency is “dismissing evidence that the shortage persists.” The lawsuits refer to the FDA’s “reckless and arbitrary decision—lacking any semblance of lawful process. The word for that in Yiddish is “chutzpah.” In English, it’s “hubris.” In plain English, it’s nonsense – dangerous nonsense.

Compounding pharmacies aren’t pharmaceutical companies. The safety and effectiveness of their drugs aren’t tested by the FDA and their manufacturing facilities aren’t inspected. These “compounding cowboys” don’t report adverse events to the FDA and the agency has “received reports that in some cases, compounders may be using salt forms of semaglutide, including semaglutide sodium and semaglutide acetate. The salt forms are different active ingredients than is used in the approved drugs, which contain the base form of semaglutide. The agency is not aware of any basis for compounding using the salt forms that would meet the FD&C requirements for types of active ingredients that can be compounded.” “Buyer beware” isn’t acceptable and no one should be playing Russian Roulette with unapproved, untested, unregulated drugs.

The FDA has received reports of people overdosing on compounded semaglutide, giving themselves as much as 20 times the intended dose of the medication. Posts on TikTok, YouTube and Instagram often omit information about difficult side effects and that some influencers and companies profit from the posts. This is why the FDA makes it very clear that “Patients and health care professionals should understand that the agency does not review compounded versions of these drugs for safety, effectiveness, or quality.”

Why hasn’t there been more aggressive regulatory action? Currently, the FDA can only target false or misleading posts by influencers or telehealth companies when they have an established financial relationship with the legitimate manufacturer of the drug and, in the age of social media and aggressive pharmaceutical compounding, that loophole has become an ever-expanding wormhole of dangerous behavior. The horrific Superbowl ad for these illegal products is only the most recent, brazen, and illegal manifestation of greed trumping public health.

The good news is that the agency has proposed a new rule that addresses what drugs should not be permitted for compounding. Per “Drug Products or Categories of Drug Products That Present Demonstrable Difficulties for Compounding,” those criteria are “the formulation complexity, drug delivery mechanism complexity, dosage form complexity, complexity of achieving or assessing bioavailability, compounding process complexity, and complexity of physicochemical or analytical testing of the drug product or category of drug products.” GLP-1 medicines would meet all these enhanced standards. It’s a start, but the FDA moves deliberately, while cowboy compounders, fighting for their lives, are filing lawsuits and amping up aggressive public relations programs.

The ballooning regulatory end-run to slimness also has serious systemic implications – such as slowing research into new and important uses for GLP-1 medicines. There’s mounting evidence that these medicines may potentially treat other serious conditions, but to really dig into the scientific opportunities, the legitimate manufacturers of FDA-approved semaglutide products will have to invest hundreds of millions into research and development. That’s the good news. The bad news is that if the compounding snake oil salesmen hawking their knock-off products continue their dangerous exponential growth, legitimate manufacturers may be dissuaded from undertaking these additional high-risk research programs. Cowboy compounders are just another part of the misinformation crisis facing the FDA. Actions have consequences. Attention must be paid.

Peter J. Pitts, a former FDA Associate Commissioner and member of the United States Senior Executive Service, is President of the Center for Medicine in the Public Interest and a Visiting Professor at the University of Paris School of Medicine.