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

The landscape around compounded GLP-1 medications has been complex and evolving, with the FDA taking a strong stance to protect public health. Here's a breakdown of what happened and who is still operating legally:

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

The controversy arose due to the immense popularity and subsequent drug shortages of FDA-approved GLP-1 medications like Ozempic, Wegovy (semaglutide), Mounjaro, and Zepbound (tirzepatide). When these approved drugs were in short supply, compounding pharmacies began making their own versions to meet demand.

The FDA's primary concerns and actions have been:

1. Use of Unapproved Active Pharmaceutical Ingredients (APIs): Many compounding pharmacies were using "salt forms" of semaglutide (such as semaglutide sodium or semaglutide acetate) and tirzepatide. The FDA has clearly stated that these salt forms are NOT the active ingredients used in the FDA-approved drugs and are not FDA-approved for use in compounded drugs. The FDA has not evaluated their safety or effectiveness.
2. Lack of Quality and Safety Assurance: Compounded drugs do not undergo the rigorous safety, efficacy, and quality testing that FDA-approved drugs do. This raises concerns about:
   • Purity and Potency: Whether the compounded drug contains the stated amount of active ingredient and is free from contaminants.
   • Sterility: Especially for injectable medications, ensuring they are free from harmful bacteria.
   • Manufacturing Practices: Lack of oversight on the conditions under which these drugs are made.
3. Misleading Marketing: Some companies and clinics were marketing compounded GLP-1s as "generic" versions of Ozempic or Wegovy, implying they were identical, which is not true.
4. Adverse Event Reports: The FDA received reports of adverse events associated with compounded semaglutide, though it's often difficult to definitively link these to the compounded product without specific testing.

FDA's Actions:

• Issued numerous warning letters and safety alerts to the public and healthcare providers about the risks of using compounded semaglutide and tirzepatide.
• Sent cease and desist letters to specific compounding pharmacies and online platforms that were illegally marketing or distributing these products.
• Collaborated with state boards of pharmacy to ensure compliance with compounding regulations.
• Updated their drug shortage list to specify when semaglutide and tirzepatide are or are not in shortage, as this dictates when compounding is permissible.

Who Is Still Operating Legally?

Compounding of GLP-1s is only legal under very specific and limited circumstances, primarily when there is a documented shortage of the FDA-approved drug and the compounding pharmacy uses the exact same active ingredient as the approved drug.

Here are the conditions for legal operation:

1. Presence of an FDA-Recognized Drug Shortage: Compounding is generally allowed only when an FDA-approved drug is on the FDA's official drug shortage list. As of recent updates, some dosages of Ozempic and Wegovy (semaglutide) have fluctuated on and off this list, but Mounjaro and Zepbound (tirzepatide) are generally NOT currently on the shortage list, which significantly limits the legality of compounding tirzepatide.
2. Use of the Correct Active Pharmaceutical Ingredient (API):
   • The compounding pharmacy must use the base form of semaglutide or tirzepatide, which is the API in the FDA-approved products.
   • They CANNOT legally use salt forms like semaglutide sodium, semaglutide acetate, or other non-FDA-approved forms. This is a critical distinction.
3. Valid Patient-Specific Prescription: The compounded drug must be prepared for an individual patient based on a valid prescription from a licensed healthcare provider, who has determined a medical need for the compounded medication. It cannot be compounded in anticipation of future prescriptions or for "office stock" unless the pharmacy is a 503B outsourcing facility.
4. Adherence to Compounding Regulations:
   • 503A Compounding Pharmacies: These are traditional state-licensed pharmacies that compound for individual patient prescriptions. They must follow state board of pharmacy regulations and USP (United States Pharmacopeia) standards for compounding.
   • 503B Outsourcing Facilities: These are facilities that compound in larger batches for healthcare entities (like hospitals or clinics) and have stricter FDA oversight, similar to manufacturing facilities. They also must adhere to the same API and shortage rules.

To determine if a pharmacy or clinic is operating legally when offering compounded GLP-1s, you should ask:

• "Is the FDA-approved version of this medication currently on the FDA's drug shortage list?" (If not, compounding is likely illegal.)
• "What active pharmaceutical ingredient (API) are you using? Is it the base semaglutide/tirzepatide, or a salt form (like semaglutide sodium/acetate)?" (If it's a salt form, it's not FDA-approved for compounding.)
• "Is this medication being compounded by a state-licensed 503A pharmacy or a 503B outsourcing facility?"
• "Can I see the prescription from my licensed healthcare provider for this specific compounded medication?"

In summary:

• FDA-approved GLP-1s (Ozempic, Wegovy, Mounjaro, Zepbound) are the safest and most regulated option.
• Legal compounding is a narrow lane: It requires an active drug shortage of the approved product, the use of the base active ingredient (not salt forms), and a patient-specific prescription from a licensed provider.

Recommendation for Consumers: Always prioritize obtaining FDA-approved versions of GLP-1 medications if possible. If considering a compounded version, thoroughly verify the legality and safety directly with your healthcare provider and the compounding pharmacy. Do not engage with services that promise cheap "generic" versions or use "salt forms" of these medications, as they pose significant health risks.