For much of 2023–2024, global demand for GLP-1–based weight-loss medications such as semaglutide and tirzepatide far exceeded supply. With branded products like Ozempic, Wegovy, and Mounjaro back-ordered for months, a shadow market of “compounded” or “off-brand” versions emerged almost overnight. Specialty pharmacies and telehealth start-ups began selling vials, prefilled syringes, or even oral mixtures under names that mimicked the originals. For some patients, these preparations offered the only accessible and often cheaper route to treatment. For regulators, they quickly became a source of alarm. (Which drug is better and why? Read our article.)
By mid-2025, the U.S. Food and Drug Administration (FDA) had collected hundreds of adverse-event reports tied to compounded GLP-1 drugs, ranging from severe nausea and dehydration to dosing overdoses that required hospitalization. In parallel, federal and state agencies uncovered widespread manufacturing irregularities, counterfeit active ingredients, and illegal imports of semaglutide “salt” forms never approved for human use.
The FDA’s response has been swift and unusually public. After confirming that the national shortage of branded GLP-1 drugs had largely resolved, the agency began tightening enforcement, publishing adverse-event summaries, clarifying compounding limits, and sending more than 50 warning letters to compounders and distributors. The controversy has forced a reckoning: how can the U.S. maintain safe, affordable access to GLP-1 therapies while shutting down dangerous gray-market sources?
The answer lies in balancing supply, oversight, and patient trust, an equation regulators are now scrambling to solve.
Why Now?
The FDA’s crackdown comes at a pivotal moment in the GLP-1 era. During the height of shortages in 2023–2024, compounding pharmacies filled a real gap, producing their own versions of semaglutide and tirzepatide for patients who otherwise faced months-long waits for treatment. That emergency workaround, however, persisted long after the shortage ended.
In early 2025, the U.S. Food and Drug Administration declared that supplies of the branded drugs had stabilized and moved to close the regulatory loophole that allowed wide-scale compounding. At the same time, the agency published alarming data: more than 1,100 adverse-event reports linked to compounded GLP-1 products, 605 involving semaglutide and 545 involving tirzepatide. These cases included severe gastrointestinal events, dosing miscalculations, and suspected contamination.
By mid-year, the agency had sent over 50 warning letters to compounders, telehealth vendors, and distributors marketing unapproved or counterfeit versions. Enforcement extended to online sellers and foreign ingredient suppliers. The FDA also warned of “salt forms” such as semaglutide sodium and semaglutide acetate, which are not approved for injection and can vary widely in potency.
The convergence of three factors, namely, restored supply, growing evidence of harm, and escalating online sales, has turned compounded GLP-1s from a temporary workaround into a national safety issue. In 2025, the question is no longer how to meet demand, but how to protect patients from unsafe, unregulated substitutes.
What Are Compounded GLP-1 Products?
Compounding is a long-standing and legitimate pharmaceutical practice, the custom preparation of medications by licensed pharmacists when a commercially available product cannot meet a patient’s specific needs. In principle, it is meant for individualized dosing, allergy accommodations, or temporary drug shortages. In the case of GLP-1 therapies, however, compounding has been stretched far beyond that intent.
Compounded GLP-1s are versions of drugs such as semaglutide or tirzepatide made by pharmacies that mix or reconstitute the active ingredients outside of the approved manufacturing process. They are not FDA-approved, meaning they have not undergone the rigorous quality, safety, or stability testing that brand products like Ozempic, Wegovy, or Mounjaro must pass. Some are dispensed in vials or prefilled syringes; others are marketed as “oral” or “sublingual” drops, forms never authorized by the original manufacturers. A major point of concern is chemical authenticity. Many compounders use “salt forms” that are not the same molecular entity as the approved drug. These versions may differ in absorption or potency, potentially leading to under- or overdosing. Without Good Manufacturing Practice (GMP) oversight, even small formulation errors can translate into significant biological differences.
Legally, compounding is permissible only under narrow conditions, such as a temporary drug shortage officially listed by the FDA. Once supply stabilizes, compounding large batches or marketing to the general public violates federal law. In June 2025, the FDA reiterated that the national supply of GLP-1 products had normalized and instructed compounders to cease production and distribution of semaglutide and tirzepatide versions except in rare, patient-specific cases.
Despite these warnings, online sales and telehealth promotions of “custom semaglutide” continue, often marketed with professional-looking branding that blurs the line between legitimate pharmacy practice and unregulated manufacturing.
In essence, compounded GLP-1s occupy a grey market between medical necessity and commercial opportunism, a space now under intense federal scrutiny.
Safety and Adverse-Event Evidence
The scale of the problem became undeniable in mid-2025, when the FDA published its first detailed summary of injuries and hospitalizations linked to compounded GLP-1 products. The agency reported 605 adverse events associated with compounded semaglutide and 545 events tied to compounded tirzepatide between January 2023 and July 2025. While these reports do not prove causation, their patterns paint a consistent picture of risk: severe gastrointestinal symptoms, dehydration, gallbladder inflammation, pancreatitis, fainting, and accidental overdoses from mis-dosed vials or prefilled syringes. Several cases required emergency medical care.
A deeper review revealed that the most frequent incidents stemmed from dosing errors. Unlike factory-standard pens that deliver pre-measured increments, compounded products often come in multi-dose vials requiring manual measurement with insulin syringes. Patients frequently confuse milligrams with millilitres or inject full vials instead of micro-doses. In one published case report, a patient who injected 10 mg of semaglutide instead of 0.25 mg developed severe vomiting and dehydration requiring IV fluids.
Chemical composition adds another layer of risk. Investigations by the FDA and independent laboratories found that some compounded semaglutide vials contained unverified “salt” derivatives, including semaglutide sodium and semaglutide acetate, which are chemically distinct from the approved base form. These salts may not fully convert to the active peptide in the body, raising questions about bioavailability and safety. Others were found contaminated with particulate matter or had concentrations inconsistent with their labels.
The lack of Good Manufacturing Practice (GMP) oversight compounds these hazards. FDA inspections of certain facilities uncovered improper sterile technique, inadequate microbial testing, and unvalidated stability data. In several cases, pharmacies were sourcing active ingredients from unregistered suppliers abroad, circumventing quality controls entirely.
Adverse-event reports also include substitution and counterfeit issues. Some online vendors advertised “compounded semaglutide” but shipped unapproved dietary supplements or peptides sourced from overseas bulk sellers. The FDA and customs officials have since seized multiple counterfeit shipments and issued consumer alerts warning that such products may contain no active ingredient or the wrong one.
Although compounded GLP-1s remain popular due to lower prices and easier online access, the accumulating evidence underscores that these are not benign alternatives. In the absence of manufacturing controls, potency verification, or proper labeling, the risk of unpredictable outcomes is substantial, and, as the FDA notes, “patients have no reliable way to know what they are injecting.”
Regulatory Oversight and Real-World Impact
By mid-2025, the FDA’s posture toward compounded GLP-1 products had shifted from tolerance to decisive enforcement. After confirming that supplies of brand-name Ozempic, Wegovy, and Mounjaro were stable, the agency announced that broad-scale compounding of semaglutide and tirzepatide was no longer justified under U.S. law. Only patient-specific prescriptions prepared by licensed pharmacies could continue, and only with verified, pharmaceutically equivalent ingredients.
Within months, the agency moved forcefully: publishing its dedicated alert page, FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss; releasing adverse-event data; and sending more than 50 warning letters to compounders, telehealth platforms, and bulk-ingredient distributors marketing or selling unapproved formulations. The FDA also tightened import controls after discovering adulterated semaglutide powder from unregistered foreign suppliers, while several state pharmacy boards issued their own cease-and-desist orders.
These actions carry significant ripple effects. For patients, they mean the abrupt disappearance of lower-cost compounded options that many relied on during shortages. While safety clearly demands oversight, given hundreds of reports of overdosing, contamination, and counterfeit vials, the crackdown leaves affordability gaps. Without insurance coverage, brand GLP-1 drugs can exceed $1,000 per month, creating a new form of therapeutic inequity.
Clinicians shall now help patients navigate this landscape: confirming product legitimacy, transitioning those on compounded formulations to approved versions, and reporting any adverse effects. Hospitals and payers, meanwhile, must address coverage gaps that initially fueled the gray market.
The FDA’s enforcement underscores a core dilemma in modern obesity care: safety versus access. Eliminating unsafe compounded products protects public health, but unless payers and policymakers expand coverage for approved GLP-1s, patients may again turn to the very markets regulators are trying to shut down. Sustainable safety will require not only vigilance, but affordability and transparency across the supply chain.
Future Directions & Challenges
The crackdown on compounded GLP-1s represents a necessary correction, but not the end of the story. Regulators, manufacturers, and clinicians now face the challenge of building a sustainable model for safe and equitable access.
In the short term, the FDA will continue to expand oversight, including real-time tracking of online pharmacies and tighter import restrictions for bulk peptide ingredients. Several states are introducing digital track-and-trace systems to authenticate GLP-1 supply chains, while international cooperation is increasing to intercept counterfeit shipments at ports of entry. These measures aim to prevent a resurgence of the “gray market” as new GLP-1 analogues enter circulation. Yet the deeper issue remains affordability. Without insurance reform, many patients priced out of approved therapies will continue to seek alternatives. Experts warn that enforcement alone cannot eliminate risk, it must be paired with expanded payer coverage, negotiated pricing, and clear clinical pathways for switching from compounded to approved formulations.
At the same time, education is critical. Physicians, pharmacists, and patients must understand that compounded does not mean generic, and that safety is inseparable from regulation. The FDA and professional associations are ramping up outreach campaigns to clarify what constitutes an approved GLP-1 product and how to verify authenticity.
Ultimately, the compounded-GLP-1 controversy is a preview of challenges to come: as demand for metabolic therapies surges worldwide, access, cost, and safety will remain in tension. The solution will depend on coordination, not confrontation, between regulators, industry, and the public they serve.
Conclusion
The meteoric rise of GLP-1 drugs has reshaped obesity treatment and exposed the risks of a marketplace moving faster than its safeguards. What began as a temporary fix during shortages has evolved into a widespread safety challenge, forcing regulators to confront the blurred boundaries between legitimate compounding and unregulated manufacturing.
The FDA’s actions in 2025 from publishing adverse-event data to issuing mass warning letters mark a turning point in this story. The agency’s message is unambiguous: compounded or “gray” semaglutide and tirzepatide are not generics, and their risks can be serious, even life-threatening.
But true safety will require more than enforcement. If high prices and coverage barriers persist, patients will continue seeking cheaper, riskier substitutes online. For GLP-1 therapies to fulfil their public-health promise, they must be both regulated and reachable. The current crackdown is a reminder that innovation and integrity must advance together. Protecting patients from counterfeit and compounded drugs is essential, but so is ensuring that safe, effective options remain within everyone’s reach.
References
- U.S. Food and Drug Administration. (2025, July 31). FDA’s concerns with unapproved GLP-1 drugs used for weight loss.
- U.S. Food and Drug Administration. (2025, June 25). FDA clarifies policies for compounders as the national GLP-1 supply begins to stabilize.
- U.S. Food and Drug Administration. (2025, July 15). FDA alerts health care providers, compounders, and patients to dosing errors associated with compounded injectable semaglutide and tirzepatide.
- Reuters. (2025, Sept 5). U.S. FDA tightens control over obesity-drug ingredient imports amid safety concerns.
- WSGR. (2025, Sept 16). FDA sends warning letters to more than 50 GLP-1 compounders and manufacturers.
