Compounded Medicines vs. Branded Drugs: How Today’s GLP-1 Disputes Echo Yesterday’s Hormone Battles
For more than two decades, the United States has navigated a recurring tension between two legitimate public-health aims: safeguarding the integrity of FDA-approved medicines and preserving access to individualized therapies prepared by licensed compounders. The flashpoints change—bioidentical hormones yesterday, GLP-1 receptor agonists today—but the core pattern remains strikingly similar. In both eras, brand manufacturers raised safety, quality, and marketing concerns about copies of their products, while compounders emphasized patient access and the statutory allowances that let them prepare drugs for individual needs or during shortages. Regulators, courts, and professional groups have responded with a mix of enforcement actions, policy clarifications, and guardrails that continue to define the boundary between manufacturing and compounding.
This article traces the parallels—factually and even-handedly—between (1) Wyeth’s mid-2000s campaign concerning compounded bioidentical hormone therapy (cBHT) and (2) current actions by Novo Nordisk and Eli Lilly involving compounded versions of semaglutide and tirzepatide. It also explains the legal framework that sits behind both episodes—sections 503A/503B of the Food, Drug, and Cosmetic Act (FDCA), the Drug Quality and Security Act (DQSA), and related case law—so readers can view today’s headlines in context.
A brief legal backdrop: 503A, 503B, and a key Supreme Court case
Pharmacy compounding is explicitly recognized in federal law. Section 503A (traditional pharmacy compounding) exempts qualifying compounders from certain requirements applicable to manufacturers—such as premarket approval, CGMPs, and “adequate directions for use” labeling—when the compounding is based on a valid prescription for an identified individual patient and other criteria are met. Section 503B (created in 2013) established “outsourcing facilities,” which may compound sterile drugs without individual prescriptions if they meet additional quality and reporting requirements.
Earlier, in Thompson v. Western States Medical Center (2002), the U.S. Supreme Court struck down federal restrictions that had barred compounders from advertising their services, on First Amendment grounds. Congress later revised the statutory framework via the DQSA (2013), which, among other changes, removed the invalidated provisions and formally created 503B.
Then: Wyeth and compounded bioidentical hormones (mid-2000s)
What triggered the conflict?
In 2005, Wyeth (maker of FDA-approved hormone therapies) filed a Citizen Petition urging FDA to address certain compounding practices involving cBHT. Wyeth alleged that some pharmacies were effectively copying approved drugs, making unsupported safety/efficacy claims, using unapproved ingredients such as estriol, and operating without appropriate manufacturing controls.
FDA’s response
In January 2008, FDA sent warning letters to several pharmacies, stating that claims of safety/superiority were unsubstantiated and that products containing estriol were misbranded or unapproved. FDA reiterated that compounded drugs are not FDA-approved and encouraged use of approved therapies when appropriate.
Evidence and policy follow-up
Years later, the National Academies of Sciences, Engineering, and Medicine (NASEM) reviewed cBHT. Its 2020 report, commissioned by FDA, concluded that high-quality evidence supporting clinical utility was limited and recommended caution, including more robust quality and reporting practices when cBHT is used. FDA summarized these recommendations and their implications for oversight.
The report’s methodology and panel composition were criticized by stakeholders, including the Alliance for Pharmacy Compounding (APC), which argued the process discounted clinical experience and patient outcomes. Despite the report, compounded hormones remain legal under 503A and 503B, and APC continues to advocate for their availability.
What “winning” looked like
No single court ruling or regulatory pronouncement declared a “winner.” But it is fair to observe that compounding did not disappear. Instead, the sector adapted under clearer expectations: avoid copying approved, commercially available products; avoid unsubstantiated claims; use permissible ingredients; and comply with applicable compouning conditions.
Now: GLP-1s (semaglutide, tirzepatide) — litigation during and after the shortage
How compounded GLP-1’s proliferated
From 2022–2024, FDA listed semaglutide and tirzepatide injections in shortage, which allowed certain compounding of “copies” under statutory guardrails. FDA later declared tirzepatide’s shortage resolved on December 19, 2024 and semaglutide’s on February 21, 2025, with “off-ramp” deadlines for 503A/503B entities.
Manufacturer legal actions during and after the shortage
Litigation did not wait for shortages to end. Beginning in 2023, Novo Nordisk and Eli Lilly filed suits against pharmacies, outsourcing facilities, and telehealth firms while shortage listings were still active. These complaints typically alleged FDCA-related violations and misbranding/unapproved “copies,” alongside state-law and Lanham Act theories. Courts have dismissed some of these suits—often because FDCA enforcement is reserved to the federal government under 21 U.S.C. § 337(a) and cannot be pursued privately via state-law “backdoor” claims.
Other matters have settled (e.g., Lilly’s action involving a medispa), and some newer suits remain active or have been re-framed around non-FDCA claims (e.g., consumer-protection or false-advertising allegations). In June 2025, for instance, summaries noted Lilly’s additional filings against telehealth companies and compounders post-shortage.
FDA’s parallel safety communications
In parallel, FDA issued safety notices about compounded GLP-1s—flagging dosing-error risks with multi-dose vials, labeling inconsistencies, and use of semaglutide salt forms that are not the same active moiety as in approved products.
Where things stand now
With shortages resolved and wind-down dates passed in spring 2025, FDA re-affirmed that copying approved GLP-1s is generally impermissible; courts have, in several cases, limited private FDCA enforcement while leaving room for other theories (e.g., Lanham Act or state consumer-protection) to be litigated case-by-case. Practically, lawful compounding has narrowed to individualized clinical needs not met by an available FDA-approved product, consistent with 503A/503B.
Five through-lines that connect the hormone and GLP-1 chapters
A concern about “copies” of approved medicines
In both eras, manufacturers argued that some compounders were reproducing their approved products rather than addressing genuine, individualized needs. Wyeth’s petition focused on copying hormone products, while today’s cases focus on semaglutide/tirzepatide copies—especially after shortages ended.Safety, quality, and claims
Regulators repeatedly highlight that compounded drugs are not FDA-approved and thus lack premarket review for safety, effectiveness, and quality. The 2008 BHRT warning letters targeted unsubstantiated claims; the GLP-1 communications warn about dose-measurement errors, labeling irregularities, and non-equivalent salt forms.Evidence base and the role of consensus reports
For hormones, NASEM and peer-reviewed commentary noted limited evidence supporting cBHT claims and recommended stronger quality and reporting if used. For GLP-1s, the evidence base overwhelmingly concerns the FDA-approved products; safety concerns with compounded versions reflect formulation, dosing, and sourcing variability rather than efficacy of the branded active ingredients.Lawful space for compounding—narrowed but preserved
Compounding retains a defined role: individualized therapies when no suitable FDA-approved option exists, clinically justified variations (e.g., allergy, excipient intolerance), or limited circumstances during an FDA-declared shortage—subject to 503A/503B conditions.Litigation and policy are catalysts—not endpoints
Wyeth’s petition and the 2008 warning letters did not eliminate compounded hormone use; they reset practices and expectations. Similarly, current lawsuits may clarify boundaries for GLP-1 compounding in the post-shortage market, but are unlikely to erase compounding writ large.
Important differences worth noting
Supply dynamics: The GLP-1 story has been profoundly shaped by supply-chain realities. FDA explicitly permitted limited compounding of copies during a defined shortage period and then set wind-down dates when supply was restored. The hormone episode was less about national shortages and more about ingredient status, claims, and copying.
Regulatory architecture: The 2013 DQSA created 503B outsourcing facilities and removed previously unconstitutional provisions, giving today’s FDA more tailored tools than it had during the Wyeth era.
Scope and speed: Media coverage shows the GLP-1 litigation wave is broad, multi-state, and rapid—reflecting the unprecedented demand for weight-management therapies and the rise of telehealth channels. That tempo differs from the slower, petition-driven arc of the 2000s hormone disputes.
What the record supports—and what it doesn’t
On “wins” and “losses”
It is understandable to view the hormone episode as a “win” for compounding because the practice continued after 2008, albeit with constraints; similarly, some compounders maintained a role during GLP‑1 shortages and now pivot to other individualized services. Still, neither episode produced a blanket victory. In both, FDA reaffirmed limits (e.g., copying approved products; using unapproved ingredients like estriol; misbranding or unsupported claims), and courts and Congress refined the legal guardrails. That is the consistent, documentable through‑line.
On current GLP‑1 compounding, post‑shortage
FDA’s formal determinations that tirzepatide (Dec. 19, 2024) and semaglutide (Feb. 21, 2025) shortages are resolved, coupled with wind‑down dates (February–May 2025), mean the shortage‑based rationale for compounding copies has largely sunset. Since then, manufacturers have intensified litigation, and FDA has continued to warn about safety issues (dosing, labeling, salt forms). The objective takeaway: the lawful space for GLP‑1 compounding is narrow and centers on individualized needs that cannot be met by approved products, consistent with 503A/503B.
Practical implications for stakeholders
For patients and prescribers:
When an FDA‑approved GLP‑1 is available, FDA encourages use of that product. If a compounded option is considered necessary (e.g., excipient intolerance), clinicians should ensure the prescription and compounding meet 503A/503B criteria, carefully counsel on dosing (especially with multi‑dose vials), and verify pharmacy licensure and sourcing.
For hormone therapy, clinicians should understand that evidence supporting cBHT claims remains limited, and that any use should include risk‑benefit discussions and attention to product quality.
For pharmacies and outsourcing facilities:
Adhere strictly to post‑shortage restrictions for GLP‑1s; avoid copying approved products; avoid salt forms that do not match the approved active moiety; and ensure robust labeling, documentation, and pharmacovigilance.
For hormones, avoid unsubstantiated claims and ensure ingredients and formulations align with applicable lists and standards; clearly communicate that compounded drugs are not FDA‑approved.
For manufacturers:
Litigation, petitions, and outreach remain legitimate avenues to raise safety and IP concerns, but history suggests that the durable results arise from clear regulatory guardrails and evidence‑based consensus, not exclusivity alone.
The bigger picture: a stable, but dynamic, coexistence
The U.S. system has not chosen between brand pharmaceuticals and pharmacy compounding; it has chosen both—with conditions. Approved products anchor the evidence and quality ecosystem. Compounding remains a professional service for patient-specific needs and, at times, a stopgap during shortages. When gaps close, so do the allowances.
That is why today’s GLP-1 headlines feel familiar. Wyeth’s hormone campaign led to targeted FDA actions and sustained—though bounded—compounding. Today’s GLP-1 actions by Novo Nordisk and Eli Lilly similarly aim to narrow practice to what the law allows now that shortages have ended. If history is a guide, the endpoint is neither triumph nor defeat for either side, but an equilibrium: patients retain access to individualized care within tighter guardrails, and the integrity of the FDA-approval system remains the default pathway for mass-market therapies.
The Road Ahead
Navigating the intersection of federal law, FDA guidance, and real-world patient care is complex—especially when market conditions and enforcement priorities are shifting. At Restore Health Consulting, we help 503A pharmacies, 503B outsourcing facilities, and healthcare organizations stay compliant while continuing to meet patient needs. Whether you are adapting to post-shortage GLP-1 requirements, reinforcing cBHT quality systems, or preparing for an FDA or state inspection, our expertise ensures you have clear, actionable strategies rooted in regulatory knowledge and industry best practices.
Want to explore Non-GLP-1 opportunities further?
Restore Health Consulting helps 503A and 503B operations assess and pursue opportunities apart from GLP-1s.
Contact us today to discuss how we can help your organization remain compliant, competitive, and patient-focused in a rapidly changing compounding landscape.