"The market for compounded semaglutide and tirzepatide hasn’t shrunk as many expected after the shortages ended; instead, it has remained remarkably robust, raising important questions about regulation and patient safety."
This statement from lead researcher Michael J. DiStefano encapsulates a significant finding: the market for compounded versions of popular weight-loss and diabetes medications, such as Ozempic, Wegovy, Mounjaro, and Zepbound, continues to thrive despite the resolution of official drug shortages and a renewed focus on regulatory enforcement. A recent study published in JAMA Health Forum reveals that a vast majority of weight loss clinics and medical spas are still offering these compounded alternatives, often with added ingredients, raising critical questions about product quality, regulatory oversight, and patient protection in this evolving landscape.
The Persistent Presence of Compounded GLP-1s
More than a year after federal regulators declared the shortages of semaglutide and tirzepatide to be over, compounded versions of these critical drugs are still readily available across numerous storefront weight loss clinics and medical spas. This persistent presence, detailed in a study published on July 17 in JAMA Health Forum, stands in contrast to expectations that the market would naturally contract once the supply of the original, FDA-approved medications stabilized.
Researchers from the University of Colorado Anschutz Medical Campus employed a discreet "secret shopper" methodology to investigate the market. Between August and October 2025, they conducted standardized phone inquiries to 75 brick-and-mortar establishments located in West Virginia and Oklahoma, states strategically chosen for their potential to exhibit high demand for these medications. The callers systematically inquired about the availability of specific products, their composition, the qualifications of consulting practitioners, the frequency of patient follow-ups, and the identity of the pharmacies supplying the medications.
The findings presented a consistent picture across the surveyed businesses. A striking 92.0 percent (69 out of 75) reported offering compounded semaglutide, while 86.7 percent (65 out of 75) indicated availability of compounded tirzepatide. Furthermore, 9.3 percent (7 out of 75) of these establishments were also providing oral or sublingual formulations of these drugs, suggesting a diversification of delivery methods within the compounded market.
"Our findings suggest this market didn’t shrink after the shortages ended as many expected," stated lead author Michael J. DiStefano, PhD, MBE, an assistant professor at the university’s Skaggs School of Pharmacy and Pharmaceutical Sciences. "Instead, it has remained remarkably robust, raising important questions about how these products are regulated and how patients can know whether they’re receiving medications that meet appropriate quality standards."
The regulatory context surrounding these compounded drugs is crucial to understanding the significance of these findings. The U.S. Food and Drug Administration (FDA) officially removed tirzepatide from its shortage list in December 2024 and semaglutide in February 2025. Subsequently, the FDA announced its intention to resume enforcing laws that restrict the compounding of drugs that are not experiencing shortages, with this enforcement slated to recommence after May 22, 2025. Under these regulations, compounding pharmacies are permitted to prepare patient-specific formulations for documented clinical reasons, but the routine creation of copies of commercially available products falls outside this allowance. The continued widespread sale of compounded semaglutide and tirzepatide, therefore, suggests a potential gap between regulatory intent and market reality.
The Strategic Shift Towards Additives
Perhaps the most revealing aspect of the study is not merely the persistence of the compounded drug market, but the apparent evolution of its strategy to remain viable. The research indicates that many compounding pharmacies have adapted their practices to circumvent regulatory restrictions by incorporating additives into their formulations.
The study found that 58.7 percent (44 out of 75) of the businesses surveyed confirmed that their compounded products contained an additive. By far the most common additive reported was B vitamins, present in the formulations offered by 56.0 percent (42 businesses). Levocarnitine was also found in 6.7 percent (5 businesses), and glycine in 5.3 percent (4 businesses).
The inclusion of an additional ingredient can serve as a legal maneuver, potentially allowing a pharmacy to argue that its compounded product is no longer a direct copy of an approved drug but rather a distinct, patient-specific preparation. However, the clinical justification for these added components is a separate and less clear matter. The study authors explicitly noted that the purported benefits of these additives have not been scientifically established. DiStefano directly questioned the motivations behind these additions: "One concern is whether we’re seeing clinically meaningful personalization or changes that primarily allow compounded products to remain on the market."
The researchers concluded that the FDA’s decision to resume enforcement of existing regulations may have inadvertently spurred the compounded market towards developing additive-based products rather than causing it to shrink. This strategic adaptation highlights a dynamic interplay between regulatory efforts and market innovation, with potential implications for patient access and safety.
Sterile Compounding: A Critical Safety Imperative for Injectables
The findings regarding the sourcing of these compounded medications introduce a concrete safety dimension to the discussion, a critical aspect that often remains invisible to patients. The study was able to trace the 75 surveyed businesses back to 24 distinct compounding pharmacy suppliers located across at least six different states. A thorough review of the sterile compounding license status of these facilities revealed concerning lapses in compliance. Among the 21 facilities whose licensing status could be confirmed, a significant 19.0 percent (4 facilities) were not licensed to perform sterile compounding at all.
Further investigation unearthed additional red flags. One facility had been issued two FDA warning letters since 2023, both specifically citing violations related to sterile compounding practices. Moreover, three out of 22 facilities (13.6 percent) had faced disciplinary action from their respective state boards of pharmacy.
The importance of sterile compounding cannot be overstated, particularly for injectable medications. Unlike oral medications, which are subject to the body’s natural defenses in the digestive tract and liver before entering the bloodstream, injected drugs bypass these protective barriers. GLP-1 receptor agonists are typically administered via subcutaneous injection, meaning they enter tissues or the bloodstream directly. This direct entry underscores the absolute necessity of sterile compounding, which is a distinct licensing category governed by rigorous facility standards, specialized air handling requirements, stringent testing protocols, and comprehensive personnel training.
Contamination of an injectable preparation can have severe consequences. The presence of bacteria or fungi can lead to localized infections such as abscesses at the injection site, or, in more severe scenarios, systemic bloodstream infections and sepsis. Crucially, sterility is not something a patient can visually assess; a contaminated vial can appear identical to a sterile one. This inherent inability for patients to verify the sterility of their medication places a profound reliance on the integrity and regulatory compliance of the compounding pharmacies.
The study also examined consultation patterns within these clinics. Most consultations were conducted by nurse practitioners or physician assistants (56.0 percent, or 42 out of 75 businesses), with physicians overseeing consultations in 40.0 percent (30 businesses). While a majority of businesses (69.3 percent, or 52) required an in-person consultation, and 61.3 percent (46) mandated follow-up appointments at least monthly, a concerning 22.7 percent (17 businesses) required less frequent follow-up or none at all. This is particularly relevant for GLP-1 medications, which often necessitate careful dose escalation and regular monitoring to manage efficacy and mitigate side effects.
Limitations of the Study
It is imperative to acknowledge the boundaries of this research. The study is characterized as a cross-sectional survey, meaning it provides a snapshot in time and does not investigate clinical outcomes. The researchers documented what 75 businesses in two specific states reported over a three-month period in late 2025. The study did not involve testing any of the compounded products, nor did it confirm instances of contamination or track the health outcomes of any patients who received these medications. Therefore, the study does not provide evidence of patient harm. Its primary contribution lies in identifying potential regulatory vulnerabilities within the supply chain, specifically highlighting that some sources of compounded drugs may be operating without the appropriate licenses for the types of preparations they are supplying.
Furthermore, the sample was deliberately narrow in scope. West Virginia and Oklahoma were selected for their potential high demand, and the findings may not be generalizable to states with different market dynamics, such as California or New York. The study focused exclusively on storefront clinics and medical spas, intentionally excluding the online telehealth sector, which the authors noted has historically attracted more regulatory scrutiny. Finally, as the data collection concluded in October 2025, the market landscape may have evolved since that time.
Guidance for Patients Navigating Compounded Medications
In light of these findings, DiStefano offered a crucial piece of advice for patients considering compounded GLP-1 medications: "Do not buy a compounded GLP-1 from any vendor unwilling to name the supplying pharmacy." Once the name of the pharmacy is disclosed, patients can then proactively contact their state board of pharmacy to verify its licensure status and review any disciplinary history.
Beyond this primary recommendation, patients should inquire about several practical aspects. These include whether the preparation contains additives and the rationale behind their inclusion, who will manage dose escalation, the frequency of follow-up appointments, and whether the clinic can provide documentation of the compounding pharmacy’s sterile compounding license. For individuals already using a compounded product, it is strongly advised against discontinuing or altering their regimen abruptly without professional medical guidance. Decisions regarding discontinuation or switching medications should always be made in consultation with a qualified clinician, especially for patients managing chronic conditions such as diabetes alongside weight.
Cost remains a primary driver for many individuals seeking compounded alternatives, and this is an understandable factor given the high price of brand-name medications and increasingly stringent insurance coverage policies. Before opting for a compounded source of unknown provenance, patients are encouraged to explore manufacturer-direct purchase programs and patient assistance foundations established by pharmaceutical companies like Novo Nordisk and Eli Lilly, which may offer more affordable access to approved medications.
The Evolving Regulatory Landscape and Future Outlook
The regulatory pathway for compounded semaglutide and tirzepatide is likely to become more defined. The FDA has proposed removing semaglutide, tirzepatide, and liraglutide from the 503B bulk drug substances list. This proposed change would prevent registered outsourcing facilities from compounding these drugs in bulk quantities outside of a declared shortage. However, this proposed rule would not directly govern 503A pharmacies, which are permitted to compound drugs against individual prescriptions under state board oversight.
The study authors have called for increased attention to the regulatory frameworks governing these products and for enhanced mechanisms to enable patients to verify their quality and safety. MedicalDaily will continue to monitor the FDA’s final decision on the 503B bulk list, any potential enforcement actions against the supplier facilities identified in this research, and any future studies that expand this survey beyond the two states initially examined. The ongoing scrutiny of this market underscores the critical need for transparency, rigorous oversight, and informed decision-making to protect patient health.
