Compounded GLP-1s After the Shortage: The Eight-Year-Old FDA Rule That Just Landed on the B12 Blend

FDA's April 1, 2026 update for compounders did not create a new rule for compounded GLP-1s. It took a rule FDA published in January 2018 and applied it, by name, to semaglutide combined with vitamin B12, the formulation a majority of businesses in a peer-reviewed two-state study reported offering.

That distinction decides how you read the rest of it. The four-or-fewer-prescriptions-per-calendar-month position and the ten percent strength test both appear verbatim in FDA's January 2018 Guidance for Industry, "Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act." April 2026 is where semaglutide and cyanocobalamin get written into the worked example. The policy is eight years old. The example is new.

The part of that policy that changes the arithmetic is a footnote. Footnote 20 of the 2018 guidance states that FDA "intends to consider each refill of a prescription as an additional prescription." On a drug dispensed monthly, four prescriptions in a calendar month is not four patients.

This post sets out FDA's dated record, the two spots in it that are easy to misread, what the April 1, 2026 entry added, what FDA has told companies not to say, what a peer-reviewed secret shopper study found in two states, and what a clinic can reasonably keep on file.

Every source on this page was read on 19 August 2026. We make med spa software, so we have an obvious interest in clinics keeping better client and program records. The regulatory record below holds regardless of whose software you run it in.

The dates, from FDA's own page, and the two places it is easy to misread

FDA maintains one running page, "FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize," under Drug Alerts and Statements. Entries are bracketed by date and the footer reads "Content current as of: 04/01/2026." The table reproduces the entries that set the compounding windows and flags the pairs of dates that are easiest to collapse.

The tirzepatide shortage was declared resolved twice. FDA determined it resolved on October 2, 2024, that decision was remanded as part of litigation on October 22, 2024, and FDA issued a new decision on December 19, 2024. The compounding clocks that actually ran, February 18, 2025 for 503A and March 19, 2025 for 503B, were counted from the December date.

The semaglutide 503A cutoff is the second trap. The March 2025 entry replaced the flat April 22, 2025 date with "April 22, 2025, or until the date of the district court's decision ... whichever is later." The court denied the preliminary injunction on April 24, 2025, and the April 28, 2025 entry states the period has ended.

Neither correction changes what a clinic does today. Both matter when you are reconstructing when a batch was purchased, or explaining why an arrangement that was defensible in January 2025 was not defensible in June 2025.

What the April 1, 2026 entry actually added

Three things, and none of them is a new rule.

The first is the worked example. FDA states it "may consider a compounded drug product that combines semaglutide API and another API, such as vitamin B12 (cyanocobalamin), to be essentially a copy of a commercially available drug product when the: drug products are used by the same route of administration ... drug products are the same, similar or easily substitutable strength," where "the amounts of semaglutide and vitamin B12 in the compounded drug product are within 10% of the strengths of the respective commercially available drug products."

The second is the list status: "Tirzepatide and semaglutide do not currently appear on the 503B bulks list or on FDA's drug shortage list." That is a snapshot dated April 1, 2026, not a permanent state. The third is the four-prescription statement, below.

What did not change is the test. The January 2018 503A guidance already said FDA "generally intends to consider two drugs to have a similar dosage strength if the dosage strength of the compounded drug is within 10% of the dosage strength of the commercially available drug product." It already carried a section titled "Same Characteristics as Two or More Commercially Available Drug Products," giving the template: a compounded product combining drug X and drug Y "in strengths that are within 10% of the strengths of the respective commercially available products" is one FDA generally intends to consider essentially a copy. April 2026 is that template with semaglutide and cyanocobalamin substituted in.

The statute behind it is 21 U.S.C. 353a, FDCA section 503A, text in effect August 19, 2026. Subsection (b)(1)(D) bars compounding "regularly or in inordinate amounts" any drug products that are essentially copies of a commercially available drug product. Subsection (b)(2) carves out a change "made for an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner."

The four-prescription line, and the footnote that decides the math

FDA's April 1, 2026 entry states that FDA "has stated, at this time, it does not intend to take action against a compounder for compounding a drug product that is essentially a copy of a commercially available drug product regularly or in inordinate amounts if the compounder fills four or fewer prescriptions of that compounded drug product during a calendar month."

Read the hedges. "At this time" and "does not intend to take action" describe enforcement discretion, which FDA can revise. The same words appear in the January 2018 guidance, which is stamped "Contains Nonbinding Recommendations."

Then the footnote. Footnote 20 of that guidance states that FDA "intends to consider each refill of a prescription as an additional prescription." Compounded GLP-1s are typically dispensed monthly. Under that reading, four prescriptions in a calendar month is closer to four patient-months than to four patients, and a program with a dozen active patients on monthly refills is not inside the number in any month.

There is a documented lever, and it is a documentation practice rather than a volume cap. The January 2018 guidance states that prescriptions carrying a prescriber determination of significant difference "would not be counted towards the four prescriptions." That maps onto 21 U.S.C. 353a(b)(2), which puts the determination in the hands of the prescribing practitioner for an identified individual patient. The consequence for a clinic is that the reasoning has to exist as a record written at the time, not reconstructed later.

The two website strings FDA quoted in a med spa warning letter

On September 9, 2025, FDA's Center for Drug Evaluation and Research issued a warning letter to Invigorate Med Spa in Pennsylvania, MARCS-CMS 715872, signed by George Tidmarsh, M.D., Ph.D., Director of CDER. The page is marked content current as of 09/16/2025.

The claims FDA quoted from the clinic's website were "Semaglutide (Wegovy)" and "Tirzepatide/B12 (Mounjaro)." FDA's stated theory: "Compounded drug products are not FDA-approved. Your claims imply that your products are the same as an FDA-approved product when they are not." The cited violations are misbranding under FDCA sections 502(a) and 502(bb), with introduction into interstate commerce prohibited by 301(a).

Two qualifications belong with that. FDA disclaimed exhaustiveness twice, writing that the claims identified "do not represent an exhaustive list of misbranding violations" and that the violations cited "are not intended to be an all-inclusive statement of violations that may exist." The two quoted strings are the claims FDA chose to print, not a guarantee that nothing else was at issue. And this is a misbranding action, not an essentially-a-copy action. Different legal theories, and they should not be blended.

The detail worth sitting with is the second string. "Tirzepatide/B12 (Mounjaro)" is a B12 combination product, advertised by a med spa, quoted by FDA in September 2025. Under seven months later FDA's April 1, 2026 entry uses a GLP-1 combined with vitamin B12 as its worked example of what may still be essentially a copy. The formulation in the enforcement record and the formulation in the policy example are the same shape of product.

What FDA has told companies not to claim about compounded drugs

FDA maintains a page of reminders titled "FDA to Telehealth Companies: What to Know When Promoting Compounded Drugs," under Drugs, Human Drug Compounding, content current as of 06/15/2026. It is a page of reminders, not a guidance document in FDA's term-of-art sense, and FDA addresses it to telehealth companies rather than to med spas generally. The misbranding provisions behind it, FDCA 502(a) and 502(bb), are not limited to telehealth.

The table reproduces the five practices FDA lists, in FDA's own words, alongside wording that avoids the same implication. The right-hand column is our phrasing, not FDA's, and it is not legal advice.

The last row quietly rewrites a lot of med spa marketing copy. FDA's own sentence is "FDA does not approve or license any facility." There is no such thing as an FDA-approved compounding pharmacy, an FDA-licensed pharmacy or an FDA-authorized compounder. Pharmacies are licensed by state boards. Outsourcing facilities register with FDA under section 503B, which is registration, not approval.

The second row is what the Invigorate Med Spa letter turned on. A parenthetical brand name next to a compounded ingredient is the shortest available way to imply sameness, and it is the exact string FDA quoted.

On March 3, 2026, FDA announced 30 warning letters to telehealth companies "for making false or misleading claims regarding compounded GLP-1 products offered on their websites." The release names two primary violation types: "making claims implying sameness with FDA-approved products and obscuring product sourcing by advertising drug products branded with the telehealth firm's name or trademark without qualification, implying they are the compounder." It describes this as the second group of such letters since a September crackdown on misleading direct-to-consumer pharmaceutical advertising. Both violation types are website copy, findable by anyone with a browser.

What a peer-reviewed secret shopper study found in two states

DiStefano MJ, Tilley A and colleagues published "Postshortage Compounded GLP-1 RA Market in 2 States With Potentially High Demand" in JAMA Health Forum, 2026;7(7):e262207, doi:10.1001/jamahealthforum.2026.2207. It is a cross-sectional secret shopper study of brick-and-mortar weight-loss clinics and medical spas, conducted August to October 2025, covering 75 businesses in West Virginia and Oklahoma.

Read the design before the numbers. The two states were purposively selected, not randomly sampled, on adult obesity prevalence above 35 percent, Medicaid not covering GLP-1 receptor agonists for obesity, and either high uninsured rates or high Medicare coverage. Every figure is a self-report from business staff on a phone call, and the authors list among their limitations that "respondents may have provided inaccurate information." The study was funded by the National Institute for Health Care Management Foundation. The lead author reported grants from the Institute for Clinical and Economic Review, the National Pharmaceutical Council and the PhRMA Foundation, and a co-author reported speaking fees from Sanofi, Amgen and Eli Lilly among others. Eli Lilly manufactures tirzepatide. None of that invalidates the findings. It does mean these are two-state figures with an interest disclosed, not a national rate.

The denominators shift row to row, and the paper prints them that way. The sterile-licensure finding is 4 of 21, not 4 of 23. The state-discipline finding is 3 of 22. Merging those into a single rate misstates the paper.

The 56.0 percent line is what ties this study to FDA's April 2026 example. In these two states, a majority of the businesses offering a compounded GLP-1 reported offering it combined with B vitamins. FDA's worked example of a product it may consider essentially a copy is a GLP-1 combined with vitamin B12. The example is not an edge case. It describes the shape of the majority offering in this sample.

The supplier rows are what a clinic can act on directly. A fifth of the suppliers whose licensure could be established here were not licensed for sterile compounding, and injectables are sterile products. That is a question you can answer about your own supplier this week, from the state board's license lookup.

Sourcing: state licensure, 503B registration, and what FDA does not do

Because FDA "does not approve or license any facility," a supplier's standing rests on two other things: the licence issued by a state board of pharmacy, and, for outsourcing facilities, registration with FDA under section 503B. Separate statuses, separate registers, and neither is an FDA endorsement of a product.

The 503A and 503B distinction changes what the essentially-a-copy analysis looks like. Section 503A covers a licensed pharmacist or physician compounding for an identified individual patient based on receipt of a valid prescription order, the language of 21 U.S.C. 353a(a). The four-or-fewer-prescriptions position and the ten percent strength test both sit in FDA's 503A guidance. FDA's separate January 2018 guidance on essentially-copies under section 503B, read on 19 August 2026, does not carry those two policies. Outsourcing facilities compound from bulk substances that appear on the 503B bulks list.

The operational consequence: who compounds this, under which section, licensed by whom, is a fact about your program that belongs in writing, with the date you verified it and the register you checked. It changes without anyone telling you.

The 503B bulks list notice, and what is still undecided

On April 30, 2026, FDA announced in a news release that it "is proposing to exclude semaglutide, tirzepatide, and liraglutide on the 503B bulks list, finding no clinical need for outsourcing facilities to compound these drugs from bulk substances," with a quote attributed to Commissioner Marty Makary, M.D., M.P.H.

The document itself published the next day, and it is a Notice, not a proposed rule: "List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act," 91 Fed. Reg. 23431 (May 1, 2026), pages 23431 to 23444, Docket No. FDA-2018-N-3240. The docket number is from 2018 because this is an ongoing list process rather than a fresh rulemaking. The release and the notice are one day apart and both dates are correct for their own document.

The comment deadline moved. FDA's April 30, 2026 release invited comments "by June 29, 2026," while the Federal Register structured record gives June 30, 2026. Those two sources disagree by a day, and the point is now moot: the period was extended by "List of Bulk Drug Substances ... ; Extension of Comment Period," 91 Fed. Reg. 38719 (June 26, 2026), whose DATES section states that written comments "must be submitted by July 30, 2026."

The outcome is undecided. FDA has proposed exclusion and said it will consider submitted comments before making a final determination. Reading the record on 19 August 2026, we found no published final determination on the semaglutide, tirzepatide and liraglutide entries. That is the item to watch, and it is checkable against Docket No. FDA-2018-N-3240.

What to put on file, and what your software has to do

Be careful about where the recordkeeping duty sits. The only recordkeeping text in this area is section 5 of FDA's January 2018 503A guidance, and it is addressed to compounders: "A licensed pharmacist or physician seeking to compound a drug product under section 503A should maintain records to demonstrate compliance with section 503A(b)(1)(D)." It recommends keeping prescriber significant-difference notations and the number of essentially-copy prescriptions filled, retained "for a period of at least three years." The document is stamped "Contains Nonbinding Recommendations." These are recommendations aimed at the compounding pharmacist or physician, not a federal requirement imposed on a med spa that purchases and administers.

The table is therefore prudent practice, with the origin of each item named.

Read down the middle column and a systems requirement falls out. Your clinical record has to hold a per-patient, per-visit prescriber note you can retrieve years later, because that is where a significant-difference determination lives. Your program records have to give you a per-patient dispense and refill history with dates, because the refill footnote makes dates the unit of measurement. Your supplier records have to be dated verifications, not a PDF someone emailed you in 2024.

Marketing copy needs the same treatment as clinical copy. Every page, price list, intake form and automated message that names a product is copy an inspector can read, and the September 9, 2025 letter shows two parenthetical brand names were enough to be quoted back. Version those the way you version a consent form.

Where clinical detail sits relative to your booking and CRM records is its own decision, and we wrote about that boundary in where a med spa platform stops and an EMR starts. The operational half, per-client history, dated program records and versioned communications, lives in client management and in your booking records. If a GLP-1 program is sold as a recurring plan, billing cadence and refill cadence should reconcile against each other, which is a records question before it is a pricing question.

How to check your own program in an afternoon

Start with the website. Open every public page, landing page and price list that mentions a GLP-1 and search for a brand name in parentheses next to a compounded ingredient. That is the pattern quoted in the September 9, 2025 warning letter. Do the same for intake forms, automated reminders and social profiles, because those are pages too.

Next, the supplier. Write down the compounding pharmacy or outsourcing facility by legal name, look it up on the state board of pharmacy register in the state where it is licensed, and confirm whether it holds sterile compounding authority. If it is an outsourcing facility, confirm its 503B registration status. Record the date you checked. Never describe the result as FDA approval, because FDA states it "does not approve or license any facility."

Then the formulation. Ask your compounder, in writing, for the exact strength of each API in the product they supply. Compare both against the strengths of the commercially available products. FDA's ten percent similar-strength test, published in January 2018 and applied to semaglutide plus B12 on April 1, 2026, runs against both APIs, not just the GLP-1.

Then the count. Pull dispense and refill dates for every GLP-1 patient for the last three calendar months and read them as monthly totals, remembering that each refill counts as an additional prescription. Take it to your compounding pharmacy, because the four-or-fewer position addresses the compounder and is enforcement discretion FDA describes as its position "at this time."

Finally, the chart. For each patient, confirm you can produce the prescriber's contemporaneous reasoning for the specific formulation. Under 21 U.S.C. 353a(b)(2) the significant-difference determination belongs to the prescribing practitioner, made for an identified individual patient, and it only exists if it was written down.

Frequently asked questions

Is compounded semaglutide still legal in 2026?

The temporary enforcement discretion FDA granted during the shortage is over. FDA's page states the semaglutide injection shortage was resolved on February 21, 2025, that the 503A window ran until April 22, 2025 or the district court's decision, whichever was later, and its April 28, 2025 entry states the period of enforcement discretion has ended. Compounding still occurs under the ordinary conditions of FDCA sections 503A and 503B, including the bar in 21 U.S.C. 353a(b)(1)(D) on compounding drug products that are essentially copies of a commercially available drug product regularly or in inordinate amounts.

Can a med spa advertise Wegovy or Ozempic by name?

Naming an approved product next to a compounded one is the pattern FDA quoted in its September 9, 2025 warning letter to Invigorate Med Spa, MARCS-CMS 715872. The two website claims FDA printed were "Semaglutide (Wegovy)" and "Tirzepatide/B12 (Mounjaro)," and FDA's stated theory was that "Your claims imply that your products are the same as an FDA-approved product when they are not." FDA cited misbranding under FDCA 502(a) and 502(bb), and noted the letter was not an exhaustive list of violations. Treat brand names beside compounded ingredients as a documented enforcement risk.

Does adding B12 make a compounded GLP-1 legal?

FDA addressed that combination directly on April 1, 2026. It states FDA "may consider" a product combining semaglutide API with another API "such as vitamin B12 (cyanocobalamin)" to be essentially a copy when the products share a route of administration and the amounts of both semaglutide and vitamin B12 are within 10 percent of the strengths of their respective commercially available products. Two qualifiers matter: FDA says "may consider," not "is," and the ten percent comparison runs against both APIs. The underlying combination rule dates to FDA's January 2018 503A guidance.

What is the difference between a 503A pharmacy and a 503B outsourcing facility?

Section 503A, at 21 U.S.C. 353a(a), covers compounding by a licensed pharmacist or physician for an identified individual patient based on receipt of a valid prescription order. Section 503B covers outsourcing facilities, which register with FDA and compound from bulk substances appearing on FDA's 503B bulks list. FDA's four-or-fewer-prescriptions position and its ten percent similar-strength test both sit in its 503A essentially-copies guidance from January 2018. Its separate 503B essentially-copies guidance from the same month, read on 19 August 2026, does not carry those two policies.

Does FDA approve compounding pharmacies?

No. FDA states on its telehealth reminders page, content current as of June 15, 2026, that it is false or misleading to claim "a compounded drug is sourced from an FDA-approved or FDA-licensed pharmacy or outsourcing facility. FDA does not approve or license any facility." Pharmacies are licensed by state boards of pharmacy. Outsourcing facilities register with FDA under section 503B, and registration is not approval. Describe your supplier by its state licence and, where applicable, its 503B registration status, with the date you verified each.

Does four prescriptions a month mean four patients?

No. Footnote 20 of FDA's January 2018 503A essentially-copies guidance states that FDA "intends to consider each refill of a prescription as an additional prescription." On a monthly injectable that makes the unit closer to a patient-month than a patient. The same guidance states that prescriptions carrying a prescriber determination of significant difference "would not be counted towards the four prescriptions." The four-or-fewer position is enforcement discretion, phrased by FDA as what it "does not intend" to do "at this time," and it addresses the compounder.

Can the good faith exam for a weight-loss program be done by telehealth?

That is a state question, not a federal one. A full-text search of the eCFR run on 19 August 2026 returns zero results for semaglutide, so GLP-1 receptor agonists sit outside the federal controlled-substance schedules at 21 CFR Part 1308, and the federal telemedicine framework for controlled substances does not reach them. Good faith examination and telehealth relationship rules are set by individual state medical boards and statutes and vary by state. We found no single nationwide rule. Check the medical practice act and board rules in each state where you treat.

What is still pending on the 503B bulks list?

FDA proposed on April 30, 2026 to exclude semaglutide, tirzepatide and liraglutide from the 503B bulks list, finding no clinical need for outsourcing facilities to compound them from bulk substances. The document is a Notice at 91 Fed. Reg. 23431 (May 1, 2026), Docket No. FDA-2018-N-3240. The comment period was extended to July 30, 2026 by 91 Fed. Reg. 38719 (June 26, 2026). FDA said it will consider submitted comments before making a final determination, and reading the record on 19 August 2026 we found no published final determination.