The GLP-1 Shortage is Over: Why is Compounding Still Legal?

"Wait, I thought compounded semaglutide was going away?" It's a question we hear constantly. The FDA officially ended the semaglutide shortage in February 2025—yet compounded versions remain widely available. Here's why.

The Timeline: What Actually Happened

The Two Paths to Legal Compounding

Federal law allows compounding under two main circumstances:

Path 1: Drug Shortage (Closed)

During a shortage, compounders can produce medications—including copies of commercially available drugs—to fill the supply gap. This is what allowed widespread GLP-1 compounding during 2023-2024.

Status: This path is now closed. Neither semaglutide nor tirzepatide is on the shortage list.

Path 2: "Significant Difference" (Open)

Under Section 503A of the FD&C Act, compounding pharmacies can create patient-specific medications that are NOT "essentially a copy" of a commercially available drug. If a prescriber determines that a change creates a "significant difference" for the patient, compounding is allowed.

Status: This is how compounding continues today.

What Creates a "Significant Difference"?

The FDA has never published a clear definition. Compounders rely on various modifications:

• Adding ingredients: B12, L-carnitine, glycine, etc. A "semaglutide + B12" formulation is arguably a different product than plain semaglutide.
• Different delivery methods: Sublingual drops or troches instead of injections.
• Different concentrations: Doses not available in commercial products.
• Different salt forms: Semaglutide sodium vs. semaglutide base (though this is more legally contested).

Learn more: The B12 Loophole Explained

The Legal Battles

Compounding pharmacy organizations didn't go quietly. Here's what happened:

The Outsourcing Facilities Association (OFA) Lawsuit

503B outsourcing facilities sued the FDA, arguing:

• The FDA failed to account for the 2+ million patients being served by compounders
• Brand manufacturers couldn't absorb this volume without creating a new shortage
• The shortage resolution should have required public notice and comment

Court Rulings

Federal courts sided with the FDA:

• March 2025: Court denied preliminary injunction for tirzepatide
• April 2025: Court denied preliminary injunction for semaglutide

The courts found that the FDA's decision was supported by inventory data from manufacturers and followed proper statutory definitions.

503A vs. 503B: Different Rules Apply

The shortage ending affected different pharmacy types differently:

503B Outsourcing Facilities

These FDA-registered facilities face stricter limits. Without a shortage, they generally cannot compound GLP-1s unless the drugs are on the FDA's "difficult to compound" list (they're not).

Result: Most 503B facilities have stopped producing semaglutide and tirzepatide.

503A Pharmacies

Traditional compounding pharmacies have more flexibility. They can compound patient-specific prescriptions when a prescriber determines a clinical need—including formulations with "significant differences."

Result: Most compounded GLP-1s now come from 503A pharmacies.

This is an important shift. 503B facilities have more rigorous testing requirements and FDA oversight. With most compounding moving to 503A pharmacies, quality verification becomes more important. Learn the differences.

What the FDA Says

The FDA's official position:

• Compounding "essentially a copy" of semaglutide or tirzepatide is no longer permitted
• Compounding with salt forms (semaglutide sodium, semaglutide acetate) is not supported—these are "different active ingredients"
• The agency has issued warning letters to some compounders for various violations

What the FDA hasn't done:

• Issued blanket enforcement against all GLP-1 compounding
• Published specific guidance on what constitutes a "significant difference"
• Shut down the "semaglutide + B12" approach specifically

The Current Reality (November 2025)

Here's where things stand:

What Could Change?

The current situation isn't guaranteed to last. Potential changes:

• FDA enforcement: The agency could issue clearer guidance or take action against the "significant difference" approach.
• Court rulings: Future litigation could clarify what's permitted.
• Legislative action: Congress has shown interest in drug pricing; compounding access could be affected.
• Manufacturer action: Eli Lilly and Novo Nordisk continue pursuing trademark and other legal claims against compounders.

What This Means for Patients

1. 1. Compounded GLP-1s are still available.

   Despite the shortage ending, you can still access compounded semaglutide and tirzepatide from many providers.

2. 2. Most come from 503A pharmacies now.

   Quality verification is more important than before. Look for providers with strong pharmacy partnerships and voluntary certifications.

3. 3. Formulations may include added ingredients.

   B12 or other additions aren't just marketing—they serve a regulatory purpose.

4. 4. The landscape could shift.

   If you're planning long-term GLP-1 use, be aware that availability could change.

The Bottom Line

The GLP-1 shortage is over, but compounding continues under a different legal framework. Instead of the "shortage exception," pharmacies now rely on the "significant difference" rule—creating formulations that aren't exact copies of brand-name products.

This means compounded GLP-1s remain accessible, but the regulatory foundation is less certain than it was during the shortage. If you're using or considering compounded semaglutide or tirzepatide, choose a reputable provider, understand the formulation you're getting, and stay informed as the situation evolves.