Introduction
The explosive demand for GLP-1 receptor agonists such as semaglutide and tirzepatide has reshaped obesity and diabetes care in the United States. Yet the popularity of these medications far outpaced manufacturing capacity from 2022 through 2024, leading to persistent shortages. During this period, compounding pharmacies stepped into the gap, offering customized or off-label formulations that patients could access when branded products like Wegovy, Ozempic, and Mounjaro were unavailable. While some compounders followed regulatory standards, others operated in a regulatory gray zone, producing drugs of uncertain quality and fueling a parallel “gray market.”
In February 2025, the Food and Drug Administration (FDA) announced the official end of the national semaglutide shortage, signaling that manufacturers had stabilized supply chains. By September 2025, the agency issued new clarifications and warnings: compounded GLP-1s were no longer justified in most circumstances, and unapproved products, particularly those using semaglutide salt forms, were explicitly deemed unsafe.
This article explores how FDA policy shifted once supply stabilized, the agency’s clarified stance on GLP-1 compounding, and the implications for patients, providers, and the broader pharmaceutical market.
From Shortage to Stabilization
The surge of interest in GLP-1 receptor agonists was unlike anything the obesity and diabetes drug markets had seen before. Beginning in late 2021 and accelerating through 2023, medications such as semaglutide (sold as Wegovy and Ozempic by Novo Nordisk) and tirzepatide (Mounjaro and Zepbound, marketed by Eli Lilly) became household names. Initial approvals for type 2 diabetes quickly gave way to weight-management indications, driving patient demand across the United States. Social media, celebrity endorsements, and compelling clinical data only amplified demand, overwhelming production capacity. For patients, the shortage was not abstract. Pharmacies routinely reported back orders, and clinicians struggled to maintain continuity of care for individuals who had initiated therapy but could not refill prescriptions. The stakes were particularly high for those using GLP-1s for diabetes management, where sudden interruptions could destabilize blood sugar control. For patients using them for obesity, interruption meant stalled weight loss and, in some cases, rapid regain.
Compounding during the shortage
In response, compounding pharmacies became a crucial, if controversial, source of supply. Under the Federal Food, Drug, and Cosmetic Act (FDCA), 503A pharmacies can compound medications for individual patients based on prescriptions, while 503B outsourcing facilities may produce larger batches under stricter oversight. During drug shortages, the FDA typically exercises enforcement discretion, allowing compounders to prepare versions of drugs that are otherwise commercially available.
From 2022 through 2024, this flexibility meant that pharmacies could legally compound semaglutide and tirzepatide when branded versions were on the FDA’s official shortage list. Many patients obtained compounded GLP-1s through local pharmacies or mail-order telehealth services. However, quality and consistency varied. Some compounders used salt forms such as semaglutide sodium or semaglutide acetate, which were never part of approved formulations. Others offered injectables or oral suspensions without robust data on stability or absorption. This period also saw the rise of a gray market: online sellers and clinics promoting compounded GLP-1s outside regulated channels. While some advertised legitimate products, others marketed untested mixtures, raising safety risks. The FDA received multiple reports of adverse events tied to unapproved formulations, underscoring the tension between patient access and drug safety.
Stabilization of supply in 2025
By early 2025, the supply picture began to shift. Novo Nordisk and Eli Lilly had invested heavily in scaling up production facilities, expanding manufacturing in the U.S. and abroad. In February 2025, the FDA announced the official end of the semaglutide shortage, removing it from the agency’s drug shortage list. This milestone meant that branded products were once again widely available through standard distribution channels.
The removal had immediate regulatory consequences. The legal basis for widespread compounding during the shortage no longer applied. While pharmacies could still prepare compounded versions in rare cases of documented medical need, such as patients with allergies to excipients in branded products, routine compounding of semaglutide or tirzepatide for general distribution was no longer permissible. This marked a turning point for the market. Patients who had relied on compounded versions now faced the prospect of transitioning back to branded drugs, often at significantly higher cost. Telehealth companies that had built business models around compounded GLP-1s needed to adapt or exit the market. Compounders themselves were caught between patient demand and FDA scrutiny.
The shift from leniency to enforcement
The FDA’s February 2025 announcement was not only about supply stabilization; it was also a warning that the era of regulatory leniency was ending. The agency signaled that compounded GLP-1s would be treated like other non-shortage drugs, subject to the usual restrictions. In effect, what had been tolerated during crisis conditions would now invite enforcement.
For many observers, this shift was expected but still disruptive. Patients had grown accustomed to compounded versions, sometimes at half the cost of branded products. Providers faced uncomfortable conversations about why those prescriptions were no longer appropriate or legal. The pharmaceutical manufacturers, by contrast, welcomed the stabilization, regaining control of their intellectual property and reinforcing product quality standards.
In short, the stabilization of GLP-1 supply in 2025 closed one chapter and opened another. Compounding had served as a temporary bridge, but with supply restored, the FDA was preparing to tighten oversight. The next step would come in September 2025, when the agency issued detailed clarifications and new warnings on compounded GLP-1s—a decisive moment in the transition from shortage-driven flexibility to post-shortage enforcement.
FDA Clarifications on Compounding Policy
When the FDA declared the semaglutide shortage over in February 2025, it set the stage for a more assertive regulatory stance. That stance became explicit in September 2025, when the agency issued new guidance and a series of warning letters that left little doubt: the compounding era for GLP-1 drugs was effectively ending. The FDA made clear that routine compounding of semaglutide or tirzepatide would no longer be considered acceptable once branded drugs were broadly available. The announcement emphasized a key principle of federal law: compounding is intended to fill clinical gaps, not to substitute for approved drugs when those drugs are commercially available. During the shortage, enforcement discretion allowed compounders to meet demand. But with supply restored, the FDA warned that continuing to prepare semaglutide and tirzepatide outside of narrow, patient-specific exceptions could lead to enforcement action. The shortage had been a justification, not a permanent policy.
One of the FDA’s sharpest clarifications concerned the use of salt forms. Some compounders had marketed “semaglutide sodium” or “semaglutide acetate,” arguing that these were functionally equivalent to semaglutide base. The FDA explicitly rejected this interpretation, stating that these are different active ingredients and not interchangeable with the approved formulations. This distinction was not just semantic; it went to the heart of safety and efficacy. Without robust clinical data, the agency could not assure that salt forms had the same pharmacological properties, absorption, or long-term safety profile.
In addition, the FDA cited risks inherent to compounded drugs in general: variability in potency, sterility concerns, and lack of rigorous quality testing. The agency pointed to adverse event reports linked to compounded GLP-1s, including cases of incorrect dosing and contamination. By reasserting these risks, the FDA sought to remind both providers and patients that compounding was never intended as a mainstream delivery channel for high-demand medications.
The September 2025 clarifications also carried implications for telehealth and online weight-loss clinics. Many of these businesses had relied on compounded GLP-1s during the shortage, building national networks of patients willing to pay cash for cheaper formulations. The FDA cautioned that such models were no longer legally defensible. By naming specific risks like unapproved formulations, non-compliant manufacturing, and misleading marketing, the agency signaled its intent to curb the proliferation of gray-market providers. Several companies quickly received warning letters, and the possibility of injunctions or product seizures loomed for those that ignored the message. For legitimate compounding pharmacies, the guidance was both a constraint and a clarification. Pharmacies could still provide compounded GLP-1s if a patient had a documented allergy to an excipient in the approved drug or if there was a demonstrable clinical need not met by the branded product. But those cases would be rare. The FDA’s message was unequivocal: the days of compounding GLP-1s as a workaround for price or convenience were over.
The clarification also had economic implications. Patients who had grown accustomed to cheaper compounded semaglutide faced sticker shock when forced to transition to branded products. Providers encountered frustration from patients unwilling or unable to pay, raising difficult questions about adherence and continuity of care. At the same time, branded manufacturers regained control over pricing and distribution, reinforcing their market dominance. Safety and regulatory certainty came at the cost of affordability.
The September 2025 statements underscored the FDA’s dual role: to protect the integrity of the drug supply and to safeguard public health. By closing the door on widespread compounding, the agency sought to eliminate risks from unapproved products, ensure patients received standardized, quality-assured formulations, and restore balance to a market destabilized by shortages and gray-market activity. Yet the decision also left unresolved tensions around cost, access, and equity — tensions that would play out in the months ahead as patients, providers, and insurers adapted to the post-shortage reality.
Implications for Patients, Providers, and the Market
The FDA’s tightening stance on compounded GLP-1 drugs carries immediate consequences for patients, clinicians, and the pharmaceutical industry. For many patients, compounded semaglutide or tirzepatide had been a lifeline during shortages, not only because it was available but also because it was cheaper than branded options. The shift to branded products means higher out-of-pocket costs, especially for those whose insurance plans impose high cost-sharing or refuse coverage altogether. Some patients may discontinue therapy, raising concerns about weight regain, worsening diabetes control, or cardiovascular risk.
Providers now face a more complex role. Physicians who once turned to compounding pharmacies as a practical solution must instead direct patients toward branded drugs, navigating insurance approvals and managing expectations about affordability. Prescribers who continue to recommend compounded versions risk liability, since the FDA has clarified that such practices are no longer defensible except in rare clinical circumstances. Pharmacists, too, are under pressure to align with federal policy or risk enforcement. For the pharmaceutical market, the stabilization of supply and crackdown on compounding consolidates control in the hands of manufacturers such as Novo Nordisk and Eli Lilly. These companies benefit from restored exclusivity, but they also inherit the challenge of meeting sustained demand while addressing public scrutiny over pricing. Telehealth companies that built models around compounded GLP-1s may pivot to other services or close altogether.
The broader implication is a sharper divide between regulatory safety and patient affordability. By eliminating gray-market products, the FDA has improved quality assurance, but it has also limited lower-cost alternatives, intensifying debates over access and equity. The market now hinges on whether insurers, policymakers, and manufacturers can strike a balance that keeps therapies both safe and attainable.
Conclusion
The end of the semaglutide shortage in February 2025 and the FDA’s clarifications in September marked a decisive shift in the regulatory landscape for GLP-1 drugs. What began as a period of flexibility during crisis when compounding pharmacies helped bridge critical supply gaps has now closed, replaced by strict enforcement and renewed emphasis on drug safety. Patients who once relied on compounded products must transition to branded medications, while providers and pharmacists must align practice with federal guidance.
The consequences are mixed. On one side, the FDA has reinforced quality standards, eliminating unsafe and untested compounded versions that proliferated in the gray market. On the other, access challenges remain, with many patients facing higher costs and insurers still reluctant to cover these therapies broadly. Pharmaceutical companies regain control of distribution and pricing, but they also face growing scrutiny over affordability and equity.
Looking ahead, the challenge is to balance the FDA’s mandate for safety with patient demand for affordable access. As supply remains stable and enforcement continues, the future of GLP-1 therapy will depend on whether insurers, policymakers, and manufacturers can deliver solutions that are both secure and sustainable. The shortage crisis may be over, but the debate over cost and accessibility is just beginning.
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