What happened with the FDA and compounded GLP-1s, and who is still operating legally?

The situation with the FDA and compounded GLP-1s (Glucagon-like Peptide-1 receptor agonists) is quite nuanced, but the FDA has taken a very firm stance.

What Happened with the FDA and Compounded GLP-1s?

GLP-1s like semaglutide (active ingredient in Ozempic, Wegovy) and tirzepatide (active ingredient in Mounjaro, Zepbound) became incredibly popular for diabetes management and weight loss. Due to shortages of the brand-name drugs and their high cost, compounded versions emerged rapidly.

Here's a breakdown of the FDA's concerns and actions:

1. Safety and Efficacy Concerns:

   • Not FDA-Approved: Compounded drugs are not FDA-approved. This means they haven't undergone the rigorous testing for safety, efficacy, and quality that brand-name drugs must pass.
   • Salt Forms vs. Base Forms: This is the biggest issue. Many compounders were using salt forms of semaglutide (e.g., semaglutide sodium) or tirzepatide (e.g., tirzepatide acetate) instead of the base forms found in the FDA-approved products. The FDA has repeatedly stated that these salt forms are not the active pharmaceutical ingredients (APIs) in the approved drugs and have not been evaluated for safety and efficacy. They consider products containing these salt forms to be "adulterated" or "misbranded."
   • Unapproved Ingredients: The FDA maintains lists of bulk drug substances that can be used in compounding. Semaglutide sodium and tirzepatide acetate are not on these lists for compounding.
   • Quality Control: Compounding pharmacies have less stringent oversight than pharmaceutical manufacturers. There have been reports of incorrect dosages, impurities, and non-sterile products from compounded versions.

2. FDA Actions:

   • Warning Letters: The FDA has sent numerous warning letters to compounding pharmacies, telehealth providers, and "med spas" marketing and distributing compounded GLP-1s, particularly those using the unapproved salt forms.
   • Consumer Alerts: They have issued warnings to the public about the risks associated with compounded GLP-1s, advising consumers to only use FDA-approved medications.
   • Legal Action: The FDA has pursued legal action, including seizure of products, against entities illegally producing or distributing these compounds.
   • Clarification on Shortages: While a drug being on the FDA's shortage list can sometimes justify compounding, the FDA has clarified that this does not permit compounders to use unapproved ingredients (like the salt forms) or to create "copies" of approved drugs when alternatives exist or when compounding isn't medically necessary due to an actual patient-specific need.

Who is Still Operating Legally?

This is the tricky part, as "legally" in the context of compounding GLP-1s often gets misinterpreted.

The most straightforward answer for legally operating GLP-1 providers are the manufacturers of the FDA-approved brand-name drugs:

1. Novo Nordisk:

   • Ozempic (semaglutide injection) for type 2 diabetes.
   • Wegovy (semaglutide injection) for chronic weight management.

2. Eli Lilly:

   • Mounjaro (tirzepatide injection) for type 2 diabetes.
   • Zepbound (tirzepatide injection) for chronic weight management.

These drugs are FDA-approved, produced under strict quality control, and prescribed by licensed healthcare providers.

Regarding compounding pharmacies, the FDA's stance makes it extremely difficult, if not impossible, for most to legally compound GLP-1s using the problematic salt forms.

For a compounding pharmacy to operate legally with GLP-1s (or any drug), they would generally need to meet these strict criteria:

• Valid Prescription: The drug must be prescribed by a licensed healthcare professional for an individual patient.
• Medical Necessity: There must be a specific clinical need that cannot be met by an FDA-approved drug (e.g., an allergy to an inactive ingredient in the brand-name drug, or a specific dosage form not commercially available).
• FDA-Approved API (Active Pharmaceutical Ingredient): They must use the exact API from the FDA-approved drug (semaglutide base, tirzepatide base), sourced from an FDA-compliant supplier. This is the critical stumbling block, as the FDA has explicitly stated that salt forms like semaglutide sodium or tirzepatide acetate are not the approved APIs.
• No "Copies": The compounded drug cannot be essentially a copy of a commercially available FDA-approved drug if that approved drug is available.
• Compliance with State and Federal Regulations: This includes regulations for 503A compounding pharmacies (regulated by state boards of pharmacy) or 503B outsourcing facilities (subject to stricter FDA oversight).

In essence, the FDA's position is that compounding GLP-1s with the salt forms is illegal. If a compounding pharmacy claims to be legally providing semaglutide or tirzepatide, it's crucial to ask exactly what API they are using. If it's anything other than the base form (which is virtually unavailable to compounders), it is not considered legal by the FDA.

Therefore, for consumers, the safest and only fully legal option for GLP-1s, based on FDA guidance, is to obtain an FDA-approved brand-name product through a valid prescription from a licensed healthcare provider and filled at a licensed pharmacy.