FDA warns compounded semaglutide may contain unapproved salt forms

On May 31, 2023, the FDA warned that some compounded semaglutide products sold in the United States may contain salt forms of the drug — semaglutide sodium or semaglutide acetate — rather than the active ingredient used in the approved medicines Ozempic, Wegovy and Rybelsus ^[1][2].

The agency described those salts as "different active ingredients than are used in the approved drugs" and said it does not have information on whether they have the same chemical and pharmacologic properties as the approved ingredient. "We are not aware of any lawful basis for their use in compounding," the FDA said ^[1]. CNN reported the agency's statement that products containing these salts "have not been shown to be safe and effective" ^[2].

Semaglutide is FDA-approved as Ozempic and Rybelsus to treat type 2 diabetes and as Wegovy to treat overweight and obesity ^[2]. Compounded drugs are not FDA-approved, and the agency does not review them for safety, effectiveness or quality before they are marketed ^[1][2].

Compounding drew attention because Ozempic and Wegovy have been on the FDA's drug shortage list since 2022. When a drug is in shortage, compounders may be able to prepare a compounded version if they meet certain requirements of the Federal Food, Drug, and Cosmetic Act, according to the agency ^[2]. The FDA said it has received reports of adverse events in people who used compounded semaglutide, though the agency has also said it cannot always determine whether a reported event was caused by the drug or by other factors ^[1][2]. Federal law does not require state-licensed pharmacies that are not outsourcing facilities to report adverse events to the FDA, so the agency says such events are likely underreported ^[1].

The FDA's warning covers a range of concerns beyond the salt forms. The agency said some compounded GLP-1 products have arrived warm or with inadequate ice packs, that compounded medicines may be dispensed in multi-dose vials that the FDA generally recommends discarding 28 days after first use, and that it is aware of fraudulent compounded semaglutide and tirzepatide carrying false label information, including pharmacy names that do not exist ^[1].

Novo Nordisk, which makes Ozempic, Wegovy and Rybelsus, said on June 20, 2023 that it had begun legal proceedings against some U.S. medical spas, weight loss and wellness clinics, and compounding pharmacies "to cease and desist from false advertising, trademark infringement and/or unlawful sales of non-FDA approved compounded products claiming to contain semaglutide" ^[2]. The company did not name the targeted businesses at that time ^[2].

In a second wave of suits reported July 7, 2023, Novo filed against four companies in federal courts in Florida and Tennessee: DCA Pharmacy in Nashville, Brooksville Rx in Tampa, and TruLife Pharmacy and WellHealth Rx in Jacksonville. None responded immediately to a request for comment ^[3]. Novo had filed similar suits the previous month against five health spas, clinics and pharmacies in Florida, New York, Tennessee and Texas ^[3].

Why it matters for patients

If a compounded semaglutide product's label does not state which form of the ingredient it contains, patients may not be able to tell whether they are receiving the same active ingredient as the approved drugs. The FDA says it does not know whether the salt forms behave the same way in the body ^[1].

The FDA states that compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug, and that patients should get a prescription from a doctor and fill it at a state-licensed pharmacy ^[1]. The agency lists warning signs for telehealth buyers, including claims that a compounded drug is the same as an FDA-approved one, deep discounts, medicine that looks different from what was pictured or previously received, no screening by a licensed doctor, no licensed doctor available to answer questions afterward, and spelling errors or incorrect pharmacy addresses on the label ^[1].

What happens next

Novo Nordisk said it will keep evaluating legal action against entities it says violate its intellectual property rights over compounded products claiming to contain semaglutide ^[2]. The FDA said it is working with state regulatory partners and will continue communicating with compounders about its concerns ^[1]. Which compounders used the salt forms, how many products are affected, and how the lawsuits will be resolved have not been reported ^[1][2][3].