FDA Proposes Limits on Compounding for GLP-1 Drugs as Safety Fears Grow
The FDA proposes to remove three GLP-1 drugs from the bulk compounding list as adverse events near 2,000 and Senator Tom Cotton demands a probe into Chinese APIs in compounded meds. Shortages have largely resolved, but safety and innovation concerns persist.
The Food and Drug Administration is intensifying its crackdown on compounded versions of GLP-1 weight loss drugs, proposing to remove semaglutide, tirzepatide, and liraglutide from the list of bulk drug substances that outsourcing facilities can use for compounding. The move follows the resolution of nationwide shortages and comes amid rising reports of adverse events and an influx of illegal ingredients from overseas.
The FDA announced it would seek to delete the three drugs from the 503B bulks list, which allows outsourcing facilities to compound medications using bulk ingredients when there is a shortage or a clinical need. FDA Commissioner stated, "When FDA-approved drugs are available, outsourcing facilities cannot lawfully compound using bulk drug substances unless there is a clear clinical need. This action reflects our responsibility to protect patients and preserve the integrity of the drug approval process."
Compounding was initially allowed during shortages of the brand-name drugs. Shortages of tirzepatide, the active ingredient in Mounjaro and Zepbound, ended in December 2024, and semaglutide, used in Ozempic and Wegovy, resolved in February 2025. Liraglutide, however, remains on the shortage list with limited availability. The FDA had previously announced a crackdown on GLP-1 copycats two months earlier, citing concerns that compounded drugs cannot be verified for quality, safety, and efficacy.
Safety concerns have mounted. As of this spring, the FDA had received nearly 1,000 adverse event reports associated with compounded semaglutide products and nearly 750 involving compounded tirzepatide. Some online sellers have even begun marketing compounded versions of retatrutide, an experimental obesity treatment that has not yet received FDA approval.
Adding to the risks, Senator Tom Cotton (R-Ark.) has demanded an FDA probe into whether illegal Chinese active pharmaceutical ingredients are infiltrating the U.S. supply of weight loss drugs. In a letter to the FDA commissioner, Cotton cited reports that between September 2023 and January 2025, authorities intercepted 195 illegal shipments of active pharmaceutical ingredients, roughly 60 originating from China and Hong Kong. The ingredients were "likely used in compounded weight loss medications," he wrote, warning that by January 2026, up to 1.5 million Americans could be using unregulated compounded medications containing potentially dangerous ingredients.
The Department of Health and Human Services recently referred telehealth company Hims & Hers to the Justice Department for potential violations over its planned sale of a compounded, non-FDA-approved weight loss drug. The FDA said it would "take decisive steps to restrict GLP-1 active pharmaceutical ingredients (APIs) intended for use in non-FDA-approved compounded drugs." Hims & Hers subsequently announced it would remove its weight loss pill from the market.
Beyond immediate safety issues, a study by the Pacific Research Institute estimates that widespread sales of unauthorized GLP-1 copycats could ultimately mean four or five fewer new medicines are developed in the future. The FDA proposed rule is open for public comment through June 29. It is estimated that 503A pharmacies, which compound under a different regulation, handle about three-fourths of the market for compounded drugs.