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The FDA's new draft guidance on compounded peptide bulk substances, published in early 2025, proposes a list of bulk drug substances that may be used in compounding. Tirzepatide and semaglutide are not on the proposed list. This omission could end most compounded versions of these GLP-1 receptor agonists within months. The guidance also addresses other peptides, including BPC-157, MK-677, Semax, and Hexarelin, but the immediate impact falls on tirzepatide and semaglutide because of their commercial scale.
Step 1: Understand the FDA's Draft Guidance and Its Scope
The draft guidance, titled "Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act," revises the list of substances that outsourcing facilities and traditional compounders may use. The FDA evaluates each nominated substance against criteria including safety, efficacy, and whether it appears in an FDA-approved drug. A 2024 analysis by the Pew Charitable Trusts found that most compounded GLP-1 products rely on bulk substances not on the positive list.
The guidance is not final. Comments are open until late 2025. But the agency's position is clear: it does not consider tirzepatide or semaglutide appropriate for bulk compounding when FDA-approved versions exist and are not in shortage. The shortage status has changed. As of March 2025, both tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) are listed as "resolved" on the FDA drug shortage database. That removes the legal pathway under Section 503A for many compounders.
Other peptides on the proposed list include BPC-157, MK-677, Semax, and Hexarelin. The FDA proposes to exclude all four. BPC-157 is a synthetic peptide derived from a gastric protein. MK-677 is a growth hormone secretagogue. Semax is a synthetic peptide developed in Russia. Hexarelin is a growth hormone-releasing peptide. None have FDA-approved drug products. The agency cites safety concerns, including lack of adequate toxicology data and reports of adverse events. A 2023 review in the Journal of Clinical Pharmacology noted that BPC-157 has been linked to anaphylaxis and MK-677 to elevated blood glucose.
Step 2: Review the Legal Framework for Compounded Peptides
Compounded drugs fall under two sections of the FD&C Act. Section 503A applies to traditional compounding pharmacies. Section 503B applies to outsourcing facilities. Both sections require that bulk drug substances used in compounding appear on a list developed by the FDA, or be components of an FDA-approved drug. For tirzepatide and semaglutide, the active pharmaceutical ingredient is not available as a standalone bulk substance for compounding. Compounders have used salt forms or research-grade peptides. The new guidance clarifies that such use is not permitted.
The FDA's 2022 final rule on bulk drug substances listed 23 substances for 503A and 503B use. Tirzepatide and semaglutide were not included. The agency has never approved a bulk drug substance for these two drugs. The draft guidance reaffirms that position. A 2024 article in the New England Journal of Medicine estimated that compounded GLP-1 products accounted for $1.2 billion in annual sales. The guidance would eliminate most of that market.
State boards of pharmacy have their own rules. Some states allow compounding of FDA-approved drugs when the commercial product is unavailable. But federal law preempts state law when the FDA has determined a substance is not suitable for compounding. The draft guidance is not a regulation, but it signals enforcement priorities. The FDA has already sent warning letters to compounders selling tirzepatide and semaglutide. Our earlier coverage of FTC warning letters on compounded GLP-1 ads shows the coordinated federal pressure.
Step 3: Assess the Impact on Tirzepatide and Semaglutide Access
If the guidance is finalized as drafted, compounded tirzepatide and semaglutide would become illegal for most pharmacies. Patients currently paying $300 to $500 per month for compounded versions would need to switch to brand-name drugs. The list price for Zepbound is $1,059 per month. For Wegovy, it is $1,349 per month. Insurance coverage is inconsistent. A 2024 Kaiser Family Foundation survey found that only 25% of employers cover GLP-1 drugs for weight loss.
The guidance does not affect FDA-approved tirzepatide and semaglutide. Those products remain available. But the cost barrier is real. Some patients may turn to unregulated sources, including online sellers of research peptides. The FDA has warned about subpotent and contaminated compounded tirzepatide. Our report on FDA findings of subpotent tirzepatide details the quality problems. The draft guidance would reduce the number of legal compounders, but not the demand.
For semaglutide, the situation is similar. Compounded semaglutide often uses the salt form, semaglutide sodium. The FDA has stated that semaglutide sodium is not the same as the approved semaglutide base. The draft guidance excludes semaglutide sodium. That closes a loophole some compounders used. The 2023 FDA warning letters to compounders selling semaglutide sodium are a precedent.
Step 4: Identify Who Is Affected
Three groups face immediate consequences. First, patients using compounded tirzepatide or semaglutide for weight loss or diabetes. They may lose access to affordable medication. Second, compounding pharmacies and outsourcing facilities. Many built their business on GLP-1 compounding. The guidance would force them to stop or shift to other products. Third, telehealth platforms that prescribe compounded GLP-1s. Their model depends on the compounding supply chain.
Physicians who prescribe compounded peptides also face new scrutiny. The draft guidance does not directly regulate prescribing, but it affects the legal availability of the product. A doctor can prescribe a compounded drug only if the pharmacy can legally make it. If the bulk substance is not on the list, the prescription cannot be filled. The FDA has not yet taken enforcement action against prescribers, but state medical boards may. A 2024 article in JAMA Network Open found that 40% of compounded GLP-1 prescriptions came from telehealth providers.
Researchers studying BPC-157, MK-677, Semax, or Hexarelin are also affected. The guidance applies to compounding for human use. It does not restrict laboratory research or animal studies. But the supply chain for research-grade peptides may tighten if manufacturers fear FDA enforcement. A 2023 review in Peptides noted that Hexarelin research has stalled due to limited funding and regulatory uncertainty. The draft guidance adds another barrier.
Step 5: Monitor the Comment Period and Final Rule
The draft guidance is open for public comment. The FDA typically reviews comments and issues a final guidance within 12 to 18 months. Stakeholders, including compounding pharmacies, patient advocacy groups, and telehealth companies, will submit comments. The final guidance may include changes. But the FDA rarely reverses course on substances it has already deemed unsafe or unnecessary for compounding.
Watch for three developments. First, the FDA's final decision on the bulk substance list. Second, any new enforcement actions against compounders selling tirzepatide or semaglutide. Third, state-level responses. Some states may attempt to preserve access through their own regulations, but federal preemption limits that. Our earlier analysis of the FDA panel's six-peptide decision shows how the agency has been moving toward stricter limits for months.
The draft guidance also interacts with the FDA's compounding policy for drugs in shortage. When a drug is in shortage, compounders may make it even if the bulk substance is not on the list. But once the shortage is resolved, that exception ends. Tirzepatide and semaglutide shortages were resolved in late 2024 and early 2025. The draft guidance makes the post-shortage rules permanent. Patients and providers should plan for a future without compounded GLP-1s.
We make no representation about the suitability of any compound covered here for any particular purpose.