Concerns Surrounding Compounded GLP-1s Mount As Shortages of Tirzepatide, Semaglutide End

In recent months, shortages of both tirzepatide (Mounjaro, Zepbound; Eli Lilly) and semaglutide (Wegovy, Ozempic; Novo Nordisk) have been deemed resolved by the FDA, following market pressure in recent years as demand for glucagon-like peptide-1 (GLP-1) receptor agonists to treat conditions such as diabetes and obesity exceeded supply. In the absence of these FDA-approved drugs, compounding pharmacies and outsourcers began to prepare their own versions of the therapies, which carry risks and concerns as these compounded drugs are not approved by regulatory authorities.^1,2,3

Compound GLP-1 medications have become a consistent presence for consumers. | Image Credit: © K KStock - stock.adobe.com

With the shortages of these drugs resolved, compounded GLP-1s remain on the marketplace, posing dangers to unknowing consumers, according to a roundtable panel moderated by Marc-Andre Cornier, MD, FTOS, president of The Obesity Society. Experts on the panel included Angela Fitch, MD, FACP, FOMA, the immediate past president of the Obesity Medicine Association; Robert Popovian, PharmD, MS, founder of Conquest Advisors; and Lowell Schiller, JD, former principal associate commissioner for policy and former acting chief counsel at the FDA.⁴

Fitch spoke to the major concerns surrounding the makeup of compound GLP-1 products. In FDA-approved GLP-1s like tirzepatide or semaglutide, there is a safe and effective active pharmaceutical ingredient (API) involved. However, this API has not yet been generically approved by the FDA, meaning that products claiming to include the same API as approved GLP-1s are misleading consumers, according to Fitch.⁴

“Compounded tirzepatide and semaglutide are really substandard products,” Fitch explained. “What we’ve been concerned about in this space is not necessarily about the compounding, but more about the fact that there isn’t a generically approved API to be able to say that that API is safe and effective.”⁴

Popovian explained that GLP-1 compounding has become “unregulated mass manufacturing,” straying away from the original purpose of drug compounding, which was to provide individual, personalized care in the form of specialized treatments. Currently, compounded products rely on deceitful consumer advertising in the form of marketing the substantially lower price compared with FDA-approved products, claiming the compounded drug is “Made in the USA,” and even promoting sublingual versions of the drug, which are further damaging the industry and putting consumers in danger, according to Popovian and Fitch.⁴

“I was very interested, and when I started noticing the advertising, I seriously thought the manufacturers had dropped their price,” Popovian explained, noting his expertise yet susceptibility to compounded GLP-1 marketing. “They got me, as an informed consumer and clinician; imagine what they’re doing to the average patient out there.”⁴

Schiller discussed the different regulatory authorities provided to drug manufacturers when a drug is in shortage compared with not in shortage. Manufacturers of compounded tirzepatide and semaglutide had the ability to produce these versions while the drugs were on the FDA shortage list, and once they were removed, the FDA notified compounders that they had a transitional period to cease production. Ultimately, compounded versions of drugs such as GLP-1s could have a place in patient treatment, but would require specific patient needs to be produced, according to Schiller.⁴

“There may be room [for compounded versions], but the question becomes, is there a specific, identified patient need for a version that’s different than the FDA-approved version? That’s going to be a patient-specific analysis,” Schiller explained.⁴

With compounded products still on the market, it remains critical for patients to be aware of the potential effects, which can even extend beyond treatment. For example, if a patient currently using a compounded GLP-1 wants to be switched to an FDA-approved product, it is not as simple as alternating a compounded drug for an approved drug, Fitch explains.⁴

“Patients don’t understand; we can’t switch people to the FDA-approved product, because we don’t know what patients have been getting with their compounded products,” Fitch noted. Another major concern with compounded versions is developing immunogenicity, in which patients mistakenly form antibodies to their own GLP-1 in their bodies, making the effects of the drug moot. Ultimately, Fitch explains how “there is something different about these compounded versions, and they’re not being produced in the same manner.”⁴

As a former official with Pfizer, Popovian remarked during the roundtable that the FDA indeed has the authority to investigate manufacturing practices of drug compounders. Building off this point, Schiller described that the FDA has the authority to examine the sanitary conditions of compounders and observe whether proper ingredients are being used. Furthermore, they can offer consumer alerts to patients, with a combination of these tools often used to crack down on illicit practices. Still, Schiller notes that the FDA would have to work in conjunction with other federal departments, such as the Department of Justice, to take legal action against compounders.⁴

Ultimately, the expert panel is confident in a bright future for GLP-1s and patient affordability of these therapies. Tackling the affordability issue should be a major focus of drug companies, with Fitch explaining that “a marginalized group of patients that are underserved are being preyed on” by way of lower prices for inferior therapies. Popovian expects competition in the form of biosimilars, generic approvals, and new GLP-1 treatments that could be orally administered, which will collectively help to lower prices. However, Popovian warns against pharmacy benefit managers and any future attempts by such companies to “manage the market to their own benefit.”⁴

“We should all be trying to get more patients access, and in an affordable way,” Fitch concluded.⁴

REFERENCES

1. Ferruggia K. FDA ends semaglutide shortage listing, contributing to ongoing legal challenges. Pharmacy Times. Published February 27, 2025. Accessed March 20, 2025. https://www.pharmacytimes.com/view/fda-ends-semaglutide-shortage-listing-contributing-to-ongoing-legal-challenges

2. Gerlach A. FDA affirms decision on tirzepatide shortage resolved, sets transition period for compounding. Pharmacy Times. Published December 20, 2024. Accessed March 20, 2025. https://www.pharmacytimes.com/view/fda-affirms-tirzepatide-shortage-resolved-sets-transition-period-for-compounding

3. Milenkovich N. Because Ned said: FDA is sued over removal of blockbuster weight loss drug from shortages list. Pharmacy Times. 2024;90(12). Published online January 1, 2025. Accessed March 20, 2025. https://www.pharmacytimes.com/view/because-ned-said-fda-is-sued-over-removal-of-blockbuster-weight-loss-drug-from-shortages-list

4. The Obesity Society. FDA-approved vs. compounded GLP-1s: Comparing safety, quality, and transparency. Webinar presented on March 19, 2025 over Zoom. Accessed March 20, 2025.