Battle Continues Over Compounded GLP-1s

The US Food and Drug Administration (FDA) has notified compounding pharmacies that the agency — at least temporarily — won’t take action against them for creating copies of the dual glucagon-dependent insulinotropic polypeptide/glucagon-like peptide 1 (GLP-1) drug tirzepatide (Eli Lilly and Company).

Meanwhile, Novo Nordisk, which makes semaglutide, has asked the FDA to add the GLP-1 to a list of drugs too difficult to compound. This would essentially put a stop to pharmacies making copies of its product, which is marketed as Ozempic for type 2 diabetes (T2D) and Wegovy for obesity.

Both tirzepatide (Mounjaro for T2D; Zepbound for obesity) and semaglutide have periodically been in shortage due to the ever-escalating demand for the drugs for weight loss. When a drug is officially in shortage, the FDA allows compounders to make copies. That has been the case for these medications.

But Novo Nordisk and Eli Lilly and Company, which makes tirzepatide, have continually warned that the copies are not equivalent to their FDA-approved products.

Tirzepatide Turnabout

In early October, as reported by Medscape Medical News, the FDA removed tirzepatide from its shortage list, causing a firestorm of protest from compounders, who said that patients still had trouble accessing the medication.

A trade group, the Outsourcing Facilities Association (OFA) and FarmaKeio, an individual compounder, sued the FDA on October 7, claiming the agency had acted illegally by not giving public notice. The tirzepatide removal, “without the due process of proper federal notice, at a time when they acknowledge that shortages still exist, is the definition of arbitrary and capricious,” said Lee H. Rosebush, the Outsourcing Facilities Association chairman, in a statement.

As a result of the court proceedings, the FDA quickly agreed to review the decision to remove tirzepatide from the shortages list and to cease most enforcement actions against compounders until 2 weeks after it had made a new determination.

The FDA outlined its new stance in an October 17 letter to the Alliance for Pharmacy Compounding (APC).

Scott Brunner, CEO of the APC, said in a statement that the FDA clarification was “wonderful news,” adding that the sudden removal of tirzepatide from the shortages list meant that compounders had to immediately stop making copies. That “left thousands and thousands of patients stranded with a prescription that could no longer be filled — and no speedy means of transitioning to the FDA-approved drug,” said Brunner.

He said compounders should still follow all FDA regulations and that they should be aware that state pharmacy boards might take a different approach. “We would hope most states would follow FDA’s lead, but we strongly urge pharmacies to check with their state board of pharmacy before they recommence compounding copies of tirzepatide injection,” he said.

Eli Lilly and Company has aggressively sued compounders, medical spas, and other entities that sell compounded versions of tirzepatide, and it warns consumers to be wary of such medications and of potentially counterfeit versions. In June, Eli Lilly and Company vowed to “continue to pursue legal remedies against those who falsely claim their products are Mounjaro, Zepbound, or ‘FDA-approved’ tirzepatide.” The company sued three medical spas and online vendors on October 21, according to Reuters.

In a statement to Medscape Medical News, an Eli Lilly and Company spokesman said, “No patient should be exposed to unapproved knockoff drugs with heightened risks, particularly when safe and effective FDA-approved medicines are available.” The spokesman said “knockoffs” could “expose patients to potentially life-threatening risks, including versions that are manipulated as to dose and form solely to try to evade legal restrictions.”

The American Society of Health-System Pharmacists (ASHP) reports that tirzepatide is not in shortage. ASHP said that according to Eli Lilly and Company, “While doses are available, some people still may experience difficulties getting their medication from their pharmacy. This can vary by location based upon supply chain dynamics that are not controlled by Lilly.”

The FDA notes on its shortages website that for all formulations of tirzepatide, “even when a medication is available, patients may not always be able to immediately fill their prescription at a particular pharmacy,” and that “patients may experience variability at a particular pharmacy location regardless of whether a drug is in shortage.”

Novo Seeks FDA Action

Only the 0.25 mg dose of Wegovy is listed in shortage by the FDA and the ASHP.

But compounders continue to make semaglutide. Novo Nordisk decided to try a new tactic to stop the copies.

On October 21, a law firm acting on behalf of Novo Nordisk petitioned the FDA to put semaglutide on the list “of drug products that present demonstrable difficulties for compounding.” In the filing, Novo Nordisk also asked that the FDA convene an advisory committee to discuss adding semaglutide to that list.

In response to a Medscape Medical News query, an FDA spokesman said that the agency had “just received this submission to the docket and is still reviewing it.”

Like Eli Lilly and Company, Novo Nordisk has been clear that it won’t tolerate the sales of non-branded semaglutide and has also sued medical spas, compounding pharmacies, and other entities selling their versions of the product. “Compounded products do not have the same safety, quality, and effectiveness assurances as our FDA-approved drugs and may expose patients to health risks,” wrote the company on its website. 

Alicia Ault is a St. Petersburg, Florida–based freelance journalist whose work has appeared in publications such as JAMA and Smithsonian.com. You can find her on X @aliciaault.