Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes, obesity, and related metabolic disorders.

Their rising popularity has intersected with the world of compounding pharmacies, especially during periods of drug shortages. Understanding the mechanisms, benefits, and regulatory and safety issues surrounding compounded GLP-1 products is essential for clinicians, patients, and policymakers. Here are six key points to consider.

1. There are two distinct types of compounding pharmacies.

Outsourcing facilities (503B facilities) are specialized types of pharmacies that are authorized to compound sterile drugs in bulk for distribution to healthcare providers, often to address shortages or specific patient needs. Unlike 503A compounding pharmacies, which prepare medications based on individual prescriptions, 503B facilities can produce large quantities without individual prescriptions, making them crucial for widespread distribution. These facilities must adhere to stringent FDA requirements, including compliance with Current Good Manufacturing Practices, registration with the FDA, and regular inspections to ensure product quality and safety. This regulatory oversight is more rigorous than the standards for 503A pharmacies, which primarily follow state pharmacy board regulations and focus on patient-specific prescriptions.

2. GLP-1 supply shortages opened the door for compounding pharmacies and outsourcing facilities.

Under Sections 503A and 503B of the Food, Drug, and Cosmetic Act, compounding pharmacies and outsourcing facilities may only produce compounded versions of a drug if there’s a shortage of the FDA-approved product, or if there is a specific medical need that cannot be met by the commercial product. During the GLP-1 shortage, this exception allowed compounding pharmacies to legally produce and dispense compounded versions of semaglutide, tirzepatide, and similar drugs.

The shortage created an environment in which new compounding pharmacies and med spas rapidly entered the market to meet demand. Some established businesses expanded their services, while others were newly created to capitalize on the opportunity. Telehealth platforms also began marketing compounded GLP-1s directly to consumers, further expanding access. State boards of pharmacy have struggled to keep up with enforcement for these new entities and the expanded volume.

3. The FDA has identified areas of concern for compounded GLP-1 products.

However, compounded drugs are not FDA-approved, regardless of which type of facility (503A or 503B) produced the compound, which means the FDA does not verify the safety, effectiveness, or quality of the compound before it is marketed. The FDA has raised several concerns about compounded GLP-1 products, including the following:

• Dosing concerns: Compounded GLP-1s often come in vials or syringes instead of prefilled pens, requiring patients to measure doses manually. This can increase the risk of dosing errors, either from patients measuring and self-administering incorrect doses of the drug, or in some cases healthcare professionals miscalculating doses of the drug.
• Contamination and impurities: Compounding pharmacies are not subject to the rigorous quality control, clinical testing, and manufacturing standards required for FDA-approved drugs. This increases the risk of contamination and impurities within the products, although this risk is expected to be reduced with batch testing at 503B outsourcing facilities. In addition, some compounding pharmacies are using salt forms of semaglutide products, which are not clinically approved.
• Misbranding: There have been instances of compounding pharmacies illegally selling unapproved GLP-1 products that are falsely labeled “for research purposes” or “not for human consumption” directly to consumers.

Adverse events for compounded products may be underreported because federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to the FDA. However, the FDA stated that many of these reported adverse events align with adverse events related to the FDA-approved versions of these products.

4. Resolution of shortages, FDA enforcement of restrictions, and growing litigation may limit compounding of GLP-1s in the future.

The FDA is now enforcing these deadlines, and compounded versions of semaglutide and tirzepatide are no longer legally available except in rare, individualized cases (such as for patients with specific allergies to ingredients in commercial products).

The manufacturers of several key GLP-1 products have filed multiple lawsuits against compounding pharmacies and telehealth companies for selling unauthorized versions of GLP-1 products and for copyright infringement. So far, the courts have ruled in favor of the manufacturers and the FDA.

Several large national telehealth providers offering obesity management programs have continued to provide compounded GLP-1 drugs by offering “personalized” versions to patients. They can do this by creating customized or nonstandard doses, adding ingredients (such as vitamins that are promoted to reduce nausea), or creating a dosage form that is administered differently (such as oral pills, gels, or drops).

5. The market is evolving as the compounding supply becomes limited.

This is especially true when the medication is used for weight loss, which is not covered by Medicare (excluded by law) or many Medicaid states (where it is not required to be covered). A large portion of commercial plans also do not cover GLP-1s for weight loss, where it is often excluded as a “cosmetic” use, or because of the potential high utilization and cost.

As described above, many compounding pharmacies have begun marketing “personalized” versions of the compounded drugs. Some telehealth providers that were marketing the compounded products are now pivoting to these individualized products, while other providers have shifted to marketing the discounted versions from certain manufacturers. One major manufacturer recently announced that it would only allow distribution of the discounted version of its GLP-1 product if the telehealth provider agreed to stop distributing compounded versions, making providers choose between compounded or manufactured versions. Some compounders also question whether the shortages are over and expect the increased demand for the manufactured products due to decreased compounding and future new indications to cause another shortage in the near future.

6. There are several potential pathways for patients losing access to compounded GLP-1s.

For patients who lose access to a compounded GLP-1 with their current provider, these are some of the options they may pivot to:

• Manufacturer savings programs: Manufacturers may offer savings cards, copay assistance, or patient assistance programs for eligible patients. These can help reduce out-of-pocket costs for brand-name GLP-1 medications. At least two manufacturers are offering a version of their products for $499 per month or less at this time for cash customers, and both offer copay assistance for customers with eligible insurance coverage, which can further reduce out-of-pocket costs for brand-name products. For cash-paying patients, one manufacturer also recently released an offer to provide the initial month of its drug for $199 (an additional discount of $300 from their $499 cash price), presumably to assist with those transitioning away from compounded products.
• Alternative weight-loss options: If GLP-1s are not accessible or not covered, patients may explore alternative options, including other FDA-approved weight-loss medications, nutrition counseling, meal replacements, behavioral support, or, in certain cases, bariatric surgery.
• “Personalized” GLP-1s from other compounding pharmacies or telehealth providers: Although many providers are discontinuing compounding due to the FDA enforcement notice, others are pivoting to the customized doses or added ingredients. Some patients may decide to seek out these compounded products instead of moving to the manufactured product or other alternatives, despite the previously mentioned areas of concern and the fact that they lack FDA approval.

As regulation, enforcement, and litigation continue to shift in the GLP-1 compounding market, stakeholders need to continue to monitor and understand how these changes impact demand, product pricing, channel options, and patient behavior.