Background

Semaglutide is a GLP-1 drug manufactured by Novo Nordisk. In 2017, FDA approved the drug to treat type 2 diabetes under the brand name Ozempic. A higher dose of the drug was later approved to treat obesity under the brand name Wegovy in 2021.

As demand increased, patients faced more difficulty accessing the drug, in part due to ongoing supply shortages. As a result, some patients have turned to compounded versions of semaglutide.

Unlike FDA-approved medications, compounded drugs face less regulation when it comes to safety and efficacy. According to endocrinologists and obesity medicine specialists, suppliers cannot ensure the safety and quality of these compounded versions of the drug, making them potentially dangerous for patient use.

Compound pharmacies "are probably using the same active pharmacological part [semaglutide], but when you combine things and you add different excipients, the effectiveness—if you don't measure that in a randomized controlled trial—will not be the same," said Ricardo Correa, the endocrinology fellowship director at the University of Arizona College of Medicine.

Novo Nordisk has also taken legal action against compounded semaglutide. In one review, high levels of known impurities and the presence of unknown impurities were found in some compounded semaglutide products.

FDA warns of dosing issues with compounded semaglutide

Last week, FDA issued an alert warning people of potential overdoses when using compounded versions of semaglutide. According to the agency, it has received reports of people giving themselves as much as 20 times more than the intended dose of the medication.

Unlike FDA-approved versions of the drug, which are dosed in milligrams and come in prefilled pens, compounded semaglutide comes in multiple-dose vials and can have varying concentrations. Compounded medications also do not have standardized instructions for their use. Some patients may be told to inject a certain number of "units," while others are told to inject a certain number of milligrams or milliliters.

In the reports received by FDA, dosing errors have resulted from patients incorrectly measuring and self-administering doses and healthcare providers "miscalculating" doses of the drug.

"Many of the patients who received vials of compounded semaglutide lacked experience with self-injections, according to the adverse event reports," FDA said. "Unfamiliarity with withdrawing medication from a vial into a syringe and coupled with confusion between different units of measurement (e.g., milliliters, milligrams and 'units') may have contributed to dosing errors."

"In one reported case, it was difficult for the patient to obtain clarity on dosing instructions from the telemedicine provider, who prescribed the compounded semaglutide, leading the patient to conduct an online search for medical advice and resulting in the patient taking five times the intended dose," FDA added.

Side effects associated with overdoses of compounded semaglutide include nausea, vomiting, abdominal pain, fainting, headache, migraine, dehydration, acute pancreatitis, and gallstones. Some patients have also required hospitalization.

According to FDA, patients should consult with a medical professional about how to correctly measure and administer the correct dose of the medication. Healthcare providers should also "be vigilant" when prescribing compounded semaglutide and should contact the compounder if they are uncertain about calculating the correct dose.

The agency has also asked compounders, healthcare providers, and patients to report any adverse events and errors related to compounded semaglutide to its MedWatch Adverse Event Reporting program.

In general, FDA said that compounded drugs should only be used by patients whose medical needs can't be met by an FDA-approved drug.

"Patients should not use a compounded drug if an approved drug is available to treat a patient," FDA said. "Patients and health care professionals should understand that the agency does not review compounded versions of these drugs for safety, effectiveness, or quality."

Advisory Board's weight-related resources

To help you address the growing use of weight management drugs, Advisory Board offers several resources:

This expert insight outlines the five biggest questions about weight management drugs and their answers. Similarly, this expert insight addresses what headlines get wrong about weight management drugs and what healthcare leaders should know instead.

Radio Advisory's Rachel Woods has also covered GLP-1 drugs on the podcast, discussing the potential future of these drugs and how they could help — or hurt — health systems' finances. Other useful resources include this expert insight on the five catalysts that will impact the future of obesity care and this research on three potential pathways for the future of obesity care.

Our weight management and obesity care resource library can also help leaders understand the current care landscape, manage innovations, and prepare for transformations in care. (Monaco, MedPage Today, 7/29; Kindelan, ABC News, 7/29; Swetlitz, Bloomberg, 7/26; Gibson, CBS News, 7/29)