Navigating Access: The Future of Compounded GLP-1 Receptor Agonists for Weight Loss

GLP-1 receptor agonists are among the most effective weight management therapies available, offering substantial reductions in body weight along with improvements in metabolic and cardiovascular health markers; however, their high cost limits access for many patients.

Over the past several years, glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and tirzepatide have emerged as breakthrough therapies in the fight against obesity and related metabolic disorders. Initially developed for type 2 diabetes, these agents have been repurposed and embraced by a broader patient population seeking meaningful weight loss and improved metabolic health. Their surging popularity has also revealed critical vulnerabilities in affordability and access.

With brand-name versions like Wegovy, Ozempic, and Mounjaro, often priced at more than $1,000 per month and limited insurance coverage, compounded versions of these agents have filled a temporary but vital gap. Recent regulatory shifts by the US Food and Drug Administration (FDA) have cast doubt on the future of compounded GLP-1 agonists, leaving patients, prescribers, and compounders in a state of uncertainty. (https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)

A Surge in Demand and a Regulatory Opening

FDA regulations under Sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act permit pharmacies to compound drug products that are on the FDA shortage list. Semaglutide and tirzepatide were added to the list in 2022 and 2023, respectively, due to supply constraints and high demand.

This designation allowed compounding pharmacies, both traditional 503A pharmacies, and FDA-registered 503B outsourcing facilities, to prepare sterile injectable formulations of these medications for patients with a valid prescription. For many patients, the result was access to affordable alternatives at a fraction of the price of branded products.

A Changing Landscape: FDA Rescinds Shortage Designation

In February 2025, the FDA removed semaglutide from the drug shortage list.¹ Tirzepatide followed in April. This regulatory change effectively prohibited pharmacies from continuing to compound these agents under the exemption based on shortages. The Agency gave pharmacies a wind-down period to cease compounding and distributing these medications. For 503A facilities, that deadline passed in April 2025. For 503B outsourcing facilities, the cutoff was May 22, 2025.

Figure 1.

The use and sales of GLP-1 agonists as well as the clinical success are unmatched in the history of weight loss products. Source: Grand View Research

These changes, though anticipated, ignited concern across the industry. Tens of thousands of patients who had successfully relied on compounded GLP-1s for access and affordability were now faced with limited options: pay out-of-pocket for brand-name drugs, seek international sources, or stop therapy altogether.

Safety Concerns Driving Enforcement

Part of the FDA’s motivation stems from growing concerns about safety.² Reports of adverse events associated with compounded semaglutide and tirzepatide have surfaced, ranging from gastrointestinal side effects to overdosing, injection site reactions, and even hospitalization. Some issues stemmed from compounding errors, inconsistent active pharmaceutical ingredient (API) forms (e.g., semaglutide sodium vs. base), or inadequate quality controls.

As of mid-2025, the FDA and other public health agencies have reported over 1,000 adverse events linked to compounded GLP-1 formulations. Though most did not result in long-term harm, the Agency cites these incidents as justification for strict enforcement of compounding regulations.^1,2,3

Although this figure may seem concerning on its own, it should be viewed in context. FDA-approved products like Wegovy, Ozempic, and Mounjaro are also linked to thousands of adverse events reported each year. Many involve well-known side effects like nausea, vomiting, diarrhea, and gallbladder problems. According to the 2023 FDA Adverse Event Reporting System Public Dashboard, semaglutide-containing products alone were associated with over 8,000 adverse events in the US. (https://www.fda.gov/drugs/fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard. (Accessed 6/1/2025)

What sets apart the adverse events reported with compounded versions is the concern over manufacturing variability and dosing inconsistency, not necessarily a higher number of events, but the increased uncertainty in product quality and composition. This distinction supports the FDA’s increased scrutiny and emphasizes its focus on sterility assurance, potency validation, and API integrity in compounded medications.

Advantages of 503B Outsourcing Facilities

Among the most trusted providers of compounded medications are FDA-registered 503B outsourcing facilities. Unlike traditional 503A pharmacies, which compound per individual prescription, 503B facilities are authorized to produce medications in bulk for healthcare office use and are subject to FDA inspections, current Good Manufacturing Practice (cGMP) requirements, and strict quality control standards, just as traditional pharmaceutical companies are.

503B facilities offer a higher level of regulatory oversight, providing several benefits, including validated sterile processes, dedicated cleanroom environments, comprehensive environmental monitoring programs, and lot-specific release testing for potency, sterility, and endotoxins. These requirements help reduce the risk of contamination or subpotent formulations, ensuring greater consistency and safety.

Throughout the GLP-1 shortage period, 503B facilities played a crucial role in supplying healthcare systems and clinics with compounded versions that met current Good Manufacturing Practice (cGMP) expectations. While not immune to FDA scrutiny, these outsourcing facilities have often provided a safer and more scalable alternative than less-regulated sources, particularly when treating high-risk patient populations.

For physicians, especially those treating patients for whom commercial products are still too expensive, FDA-regulated 503B outsourcing facilities serve as an essential and trustworthy resource. Collaborating with these facilities gives prescribers confidence in the quality of care and helps expand access to effective therapies.

Legal Boundaries and Clinical Discretion

FDA policy prohibits the compounding of drugs that are “essentially a copy” of a commercially available product. However, clinical exemptions do exist. Suppose a provider can document that a compounded version includes a significant difference for a specific patient, for example, the addition of another ingredient, a modified dosage strength, or a preservative-free formulation. In that case, compounding may still be permitted.

This provision has led some compounders to explore formulations that include additives such as glycine, levocarnitine, pyridoxine, and cyanocobalamin or that offer concentrations not currently marketed by manufacturers. These alterations must be clinically justified and carefully documented to remain compliant.

Given these exemptions, prescribers must recognize the critical role compounded alternatives continue to play in bridging the affordability and accessibility gap. Especially when working with reputable 503B outsourcing facilities, compounded medications provide a clinically sound and regulatory-compliant pathway to ensure patients receive the treatment they need. Embracing these options, when justified and appropriate, strengthens the continuum of care and supports health equity in an increasingly cost-constrained environment.

Impact on Patients and Access

The consequences for patients are not theoretical. The compounded formulations often cost between $250 and $400 per month, which is less than half the out-of-pocket price for many commercial GLP-1 products. For the uninsured, underinsured, or those denied coverage based on therapeutic indication, compounded medications are the only realistic option.

Now, many patients are facing difficult choices. Some are stretching doses, skipping injections, or turning to non-regulated online sources and international pharmacies. Others have stopped therapy despite documented benefits in weight reduction, glycemic control, and overall quality of life.

Legal Challenges and Industry Pushback

Compounding organizations and industry groups have pushed back against these efforts. The Outsourcing Facilities Association (OFA) has criticized the FDA’s actions as overly broad and insufficiently supported by data.⁴ Some compounders have challenged enforcement in federal courts, arguing that their formulations are legally distinct and medically necessary.

A Need for Balanced Solutions

The dilemma reflects broader tensions in the US healthcare system: how to ensure patient safety without stifling access to affordable treatments. Compounded GLP-1s served a role during a time of acute need. As supply stabilizes, the regulatory focus has understandably shifted to safety and compliance, but with real-world consequences for patients.

Policymakers and payors must recognize this gap. Solutions could include expanded insurance coverage for GLP-1 medications, including for obesity-related indications, which would reduce financial incentives to seek compounded alternatives. Patient assistance programs from manufacturers could be expanded to reach a broader range of low-income patients.

From a regulatory standpoint, clarity is key. FDA guidance should help distinguish between noncompliant and clinically justified compounded formulations, supporting prescribers who have legitimate reasons for seeking tailored options.

Conclusion A Time for Perspective

The public health need for safe, effective, and affordable obesity treatment has never been more apparent. GLP-1 receptor agonists are transforming the medical landscape and making major improvements in population health—but only if patients can access them.

As the regulatory window narrows on compounded formulations, stakeholders must resist polarized responses. This is not a binary debate between safety and access but a challenge to achieve both through thoughtful policy, responsible compounding, and equitable healthcare reform. Patients deserve nothing less.