FDA Proposal on Compounded Semaglutide and Tirzepatide (2026)

Table of Contents

1. What the FDA Did
2. 503A, 503B and the “503B Bulks List” Explained
3. What the Proposal Would Change
4. How the FDA Tests for “Clinical Need”
5. Semaglutide: The Nominations and the FDA’s Answers
6. Tirzepatide: The Nominations and the FDA’s Answers
7. Liraglutide: The Nomination and the FDA’s Answers
8. Shortages, Cost and Convenience: What the FDA Does Not Count
9. What the Proposal Does Not Do
10. Dates, Comment Period and Status as of 11 October 2026
11. How the Proposal Fits the FDA’s Earlier 503B Notices
12. Primary Documents
13. Key Research Papers
14. Connections

1. What the FDA Did

The FDA news release of 30 April 2026, “FDA Proposes to Exclude Semaglutide, Tirzepatide, and Liraglutide on 503B Bulks List,” states that the agency is proposing to exclude the three substances from the list, “finding no clinical need for outsourcing facilities to compound these drugs from bulk substances.” It says that after evaluating the nominations for the three substances, the FDA “did not identify sufficient evidence” to include them, and that a determination of clinical need “is based on patient safety and medical necessity under the law.”

The release quotes the FDA Commissioner, Marty Makary, M.D., M.P.H.: “When FDA-approved drugs are available, outsourcing facilities cannot lawfully compound using bulk drug substances unless there is a clear clinical need. This action reflects our responsibility to protect patients and preserve the integrity of the drug approval process while continuing to provide a transparent, science-based pathway for public input.”

The Federal Register notice, “List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act,” appeared on Friday 1 May 2026, on pages 23431–23444 of volume 91. Its action line reads simply “Notice.” It is signed by Grace R. Graham, Deputy Commissioner for Policy, Legislation, and International Affairs, and names Tracy Rupp of the Center for Drug Evaluation and Research as the contact. Its conclusion states that the FDA “tentatively finds no basis to conclude that there is a clinical need for an outsourcing facility to compound using the following bulk drug substances: semaglutide, tirzepatide, and liraglutide. Therefore, we propose not to include these bulk drug substances on the 503B Bulks List.”

The notice adds that other nominated substances “are under consideration and may be the subject of future notices.”

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2. 503A, 503B and the “503B Bulks List” Explained

Compounding is the preparation of a medicine by mixing or altering ingredients, outside the process by which a drug is approved. The numbers 503A and 503B refer to two sections of the Federal Food, Drug, and Cosmetic Act (FD&C Act) that set the conditions for two kinds of compounders:

• Section 503A covers compounding under that section, typically by pharmacies for individual patients. The notice points out that drugs compounded under 503A are exempt from current good manufacturing practice (CGMP) requirements.
• Section 503B covers outsourcing facilities. According to the notice, their products are not exempt from CGMP requirements; the facilities are inspected by the FDA on a risk-based schedule, have specific adverse-event reporting duties and other conditions; and they “may or may not obtain prescriptions for identified individual patients,” so they can supply compounded drugs to healthcare practitioners as “office stock” held ahead of patient need.

A bulk drug substance is an active pharmaceutical ingredient — the raw drug substance intended to be made into a finished medicine. Inactive ingredients are not bulk drug substances and are not placed on the list.

The 503B Bulks List is the list, set by the Secretary of Health and Human Services, of bulk drug substances “for which there is a clinical need.” As the notice explains, an outsourcing facility may compound from a bulk drug substance only if (1) the substance appears on that list, or (2) the drug compounded from it appears on the FDA drug shortage list at the time of compounding, distribution and dispensing. The FDA keeps a public web page of every substance it has evaluated, showing which were placed on the list and which were not.

A Federal Register docket is the public file, identified by a number such as FDA-2018-N-3240, in which a notice, its supporting papers and the public’s comments are collected; it can be read on regulations.gov.

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3. What the Proposal Would Change

The notice proposes a determination that semaglutide, tirzepatide and liraglutide will not be included on the 503B Bulks List. If finalized, the three substances would be listed by the FDA among those it considered and found no clinical need for. Under the rule the notice and the press release describe, outsourcing facilities would then have no route to compound these drugs from bulk ingredients except the separate shortage route: the drug compounded from the bulk substance would have to be on the FDA drug shortage list at the time of compounding, distribution and dispensing.

The notice describes the FDA’s intended next steps. After considering comments, the FDA “intends to consider whether input from the Pharmacy Compounding Advisory Committee (PCAC) on the nominations would be helpful,” although the law does not require that consultation. The agency “may finalize the proposed determination without change, or we may finalize a modification to the proposal to reflect new evidence or analysis regarding clinical need,” and it then intends to publish a final determination, with its rationale, in the Federal Register. Once a final determination is published, the notice says, the FDA will no longer consider docket comments on that substance, though interested parties may file a citizen petition.

For semaglutide and liraglutide, the notice records that the manufacturer of the approved products enclosed citizen petitions with its docket comments, and states that the FDA “intends to issue the response to the petition concurrently with the Federal Register notice” setting out its final decision on each substance.

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4. How the FDA Tests for “Clinical Need”

The notice explains that the FDA reads “bulk drug substances for which there is a clinical need” to mean that a substance may go on the list if (1) there is a clinical need for an outsourcing facility to compound the drug product, and (2) the product must be compounded from the bulk substance. Its approach follows a final guidance issued in March 2019, “Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B” (84 FR 7390).

When a nominated substance is an ingredient of an FDA-approved drug — which the FDA assumed, without deciding, for all three substances — the agency first asks two questions:

1. Does an attribute of each FDA-approved product make it medically unsuitable for certain patients with a condition the FDA has identified, and is the proposed compounded drug intended to address that attribute?
2. Must the proposed drug be made from the bulk substance rather than from an FDA-approved product?

The notice gives the reason for the first question: unless the approved drug is medically unsuitable for some patients, compounding from bulk “would unnecessarily expose patients to the risks associated with drug products that do not meet the standards applicable to FDA-approved drug products for safety, effectiveness, quality, and labeling and would undermine the drug approval process.” For the second, it notes that approved drugs have had premarket review and their makers are inspected, while the FDA “does not conduct a premarket review of the quality standards, specifications, and controls for bulk drug substances used in compounding.”

Only if both answers are yes does the FDA go on to weigh four further factors: the substance’s physical and chemical characterization, safety issues raised by its use in compounding, evidence of effectiveness, and its current and historical use. For all three substances the FDA answered the first question “no,” so it never reached the second question or those four factors. The notice states this explicitly for semaglutide: arguments about the safety and quality of the bulk ingredients “would be addressed in Part 2 of the clinical need analysis, which we do not reach here.”

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5. Semaglutide: The Nominations and the FDA’s Answers

What was nominated. Two nominations proposed compounding semaglutide as injections under the skin (subcutaneous), as sublingual and buccal (under the tongue or in the cheek) forms, and as oral tablets or capsules, in strengths “depending on medical provider requests,” plus combination injections with pyridoxine (vitamin B6) or an anti-nausea medicine. The uses named matched the approved uses — blood sugar control in type 2 diabetes, cardiovascular risk reduction, chronic kidney disease in type 2 diabetes and long-term weight reduction — and also “related health conditions as determined appropriate by medical provider,” which the FDA said it cannot evaluate because the conditions are not identified.

What is approved. The notice lists FDA-approved semaglutide injections in several strengths (some formulations containing propylene glycol, some not, including a 7.2 mg weekly dose approved after the nominations were filed) and oral tablets from 1.5 mg to 25 mg. The 25 mg tablet was also approved after the nominations were filed.

The arguments and the FDA’s responses, as the notice gives them:

• Swallowing and needles. The nominators cited difficulty swallowing and injection discomfort. The FDA wrote that it has “no reason to disagree” that difficulty swallowing is a well-documented issue, but that the nominators described concerns about routes of administration generally, not an unsuitability of the approved semaglutide products, and did not explain why the injections would be unsuitable for people who cannot swallow tablets. A cited laboratory concept paper on buccal tablets for peptide drugs, the FDA said, was not designed to assess the approved medicines.
• Higher strengths. For injection strengths above those approved at the time, the nominations gave no supporting data. The FDA also noted the published results of a phase 2 trial a nominator had cited: 8 mg and 16 mg weekly doses did not significantly improve HbA1c compared with 2 mg; 16 mg (but not 8 mg) produced significantly more weight loss than 2 mg; and adverse events and discontinuations were more frequent at the higher doses. For a proposed 50 mg oral tablet, the cited trials used a new, more absorbable formulation, and the FDA wrote that “improved outcomes from the higher strength … does not mean that the approved product does not achieve the intended clinical benefit.”
• “Hyper-responders” and lower doses. A nominator estimated that 5–15% of people are “hyper-responders” needing lower doses. The FDA found no reference supporting the figure; the trial cited (STEP 1) does not mention it, and reports that most gastrointestinal events were mild to moderate and transient. The FDA added that the nominations did not explain why lower-strength approved products, or the slower dose escalation the approved labeling already allows, could not be used.
• Propylene glycol. A nominator said propylene glycol in some approved injections increases injection-site irritation. The FDA wrote that the study cited found the injection-site experience of a formulation without propylene glycol “almost indistinguishable” from one with it, and did not find, as claimed, that 95% of patients preferred the propylene-glycol-free version. Its review of the FDA Adverse Event Reporting System (FAERS) found injection-site reactions with formulations both with and without propylene glycol, and approved propylene-glycol-free injections already exist.
• Combination products. The nominations gave no details of the proposed semaglutide–pyridoxine or semaglutide–antiemetic products, or why a patient could not take an approved semaglutide product and an approved second medicine separately.

The FDA’s tentative finding: no attribute of the approved semaglutide products makes them medically unsuitable for certain patients in a way the proposed compounded products would address.

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6. Tirzepatide: The Nominations and the FDA’s Answers

What was nominated. Tirzepatide was nominated for injection, sublingual, buccal and oral forms, for the approved uses (type 2 diabetes, weight reduction, moderate to severe obstructive sleep apnea in adults with obesity), for cardiovascular risk reduction, and for unspecified “related health conditions,” again with pyridoxine or antiemetic combinations. Example injection strengths ran from 2.5 mg/0.5 mL up to 30 mg/0.5 mL.

What is approved. According to the notice, tirzepatide is approved as single-dose pens and single-dose vials from 2.5 mg to 15 mg per 0.5 mL, and — approved after the nominations were filed — as multi-dose vials and multi-dose pens that each deliver four doses. The notice also records an approval on 19 December 2025 for pediatric patients 10 years of age and older, likewise after the nominations.

The FDA’s responses, as the notice gives them:

• Non-injected forms. No tirzepatide product is approved by mouth, under the tongue or in the cheek. The FDA wrote that the statutory standard “is clinical need—not ‘preference,’” and that the possibility of discomfort from an injection does not make the injection medically unsuitable.
• Higher strengths. For 20 mg and 30 mg per 0.5 mL, the nominations provided no supporting data and did not identify the patients who would need them.
• Lower doses. The nominations did not explain why the lowest approved strength, smaller volumes drawn from the approved vials, or a slower dose escalation could not be used. The notice quotes the approved labeling, which allows a lower maintenance dose for patients who do not tolerate one.
• Devices. The FDA noted that the nominations “do not acknowledge that tirzepatide is approved not only in auto-injectors, but also in vials.”
• Shortage. The nominators argued that approved tirzepatide products are in shortage. The FDA replied that shortages fall under a separate provision, not clinical need, and that “as of the date of this notice, FDA-approved tirzepatide drug products are not on the FDA drug shortage list.”

The tentative finding is the same as for semaglutide. The notice records that the manufacturer of the approved tirzepatide products filed a comment opposing the nomination.

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7. Liraglutide: The Nomination and the FDA’s Answers

What was nominated. One nomination proposed compounding liraglutide as an injection for the approved uses: blood sugar control in adults and children 10 and older with type 2 diabetes, cardiovascular risk reduction in type 2 diabetes with established cardiovascular disease, and chronic weight management in adults and in adolescents 12 and older.

What is approved. The notice lists three approved liraglutide injections at 18 mg/3 mL (6 mg/mL), two brand-name products and an approved generic, and notes that each contains propylene glycol.

The FDA’s responses, as the notice gives them:

• Strength. The only example strength offered, 18 mg/3 mL delivering 0.6 to 3 mg, is the same as the approved products, and the proposed doses match the approved labeling for weight management.
• Propylene glycol. Although no propylene-glycol-free liraglutide is approved, the FDA found no data suggesting that the ingredient makes liraglutide medically unsuitable for any patient. A FAERS review found injection-site reactions with both approved brand products and no such report whose narrative mentioned propylene glycol; the study cited by the nominator concerned semaglutide, not liraglutide.
• “Microdosing.” A newspaper article on microdosing trends cited in comments, the FDA wrote, contains no data showing that the approved product could not be used to obtain lower doses.

The tentative finding is again that no attribute of the approved products makes them medically unsuitable for certain patients.

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8. Shortages, Cost and Convenience: What the FDA Does Not Count

The notice states three limits on what “clinical need” covers in the FDA’s reading of the law:

• Supply problems. “FDA does not interpret supply issues, such as backorders, to be within the meaning of ‘clinical need’.” Shortages are handled by the separate shortage-list route in section 503B.
• Convenience. The FDA does not consider “convenience in administering a particular compounded drug product (e.g., a ready-to-use form).”
• Cost. Nor does it consider “the cost of the compounded drug product as compared with an FDA-approved drug product.”

The notice also says that a finding of better results at a higher dose, a patient’s preference for a different formulation, or the statement that a patient “can benefit” from a compounded version does not by itself show that the approved product is medically unsuitable. For products combining two active ingredients, the FDA writes that it generally does not expect to find clinical need unless the combination addresses an unsuitability of the approved drugs that giving each ingredient separately could not.

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9. What the Proposal Does Not Do

• It is not final. The notice describes its findings as tentative and its determination as proposed. The FDA writes that the notice “does not reflect a final Agency decision” on the arguments raised in the citizen petitions, and the press release says the agency “will consider submitted comments before making a final determination.”
• It does not concern the approved medicines. The notice evaluates compounding from bulk ingredients only. The FDA-approved semaglutide, tirzepatide and liraglutide products — including the approved generic liraglutide it lists — serve as the yardstick against which clinical need is measured; the notice makes no change to their approval or labeling.
• It concerns section 503B only. It addresses outsourcing facilities and the 503B Bulks List. It makes no determination about compounding under section 503A.
• It is not a safety ruling on compounded versions. Because the FDA stopped at the first question, the notice says it did not reach the safety, quality and effectiveness factors — including “the available evidence of effectiveness or lack of effectiveness of a drug product compounded with semaglutide.”
• It does not change the shortage route. Compounding from bulk when the drug is on the FDA drug shortage list remains a separate provision of section 503B.
• It does not decide other substances. The notice covers only these three; comments raising different substances or combinations are treated as outside its scope, and new nominations go to a separate docket, FDA-2015-N-3469.

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10. Dates, Comment Period and Status as of 11 October 2026

• 30 April 2026: FDA news release announces the proposal.
• 1 May 2026: notice published, 91 FR 23431, Docket No. FDA-2018-N-3240, with a 60-day comment period ending 30 June 2026. (The press release gave 29 June 2026; the Federal Register notice, the legal document, sets 30 June.) Section 503B requires a comment period of no less than 60 days for proposals to include substances; the notice says the FDA seeks comment on proposals not to include them as well.
• 26 June 2026: extension notice, 91 FR 38719 (FR Doc. 2026-12937). The FDA had received a request for a 60-day extension; it granted 30 days, to 30 July 2026, saying a shorter extension “appropriately balances allowing adequate time for interested persons to submit comments with avoiding significant delay of Agency action on these important issues.”
• 30 July 2026: comment period closed.

Legal status on 11 October 2026: proposed, not final. A check of the Federal Register through its public API on 11 October 2026 found no final determination on semaglutide, tirzepatide or liraglutide under section 503B, and nothing on the topic among documents then on public inspection. The only Federal Register documents on this docket in 2026 are the May notice and the June extension.

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11. How the Proposal Fits the FDA’s Earlier 503B Notices

The notice traces the 503B list back more than a decade:

• 2013–2015: nominations. The FDA first asked for nominations of bulk substances on 4 December 2013 (78 FR 72838), reopened the process on 2 July 2014 (79 FR 37747), and on 27 October 2015 (80 FR 65770) opened Docket FDA-2015-N-3469 for new nominations and comments. The semaglutide, tirzepatide and liraglutide nominations sit in that docket.
• 2018–2023: a series of notices. The FDA published proposals and determinations on other nominated substances on 28 August 2018, 4 March 2019, 3 September 2019, 31 July 2020, 24 March 2021, 27 January 2022, 23 November 2022, 6 April 2023 and 21 August 2023.
• March 2019: the evaluation guidance setting out the “clinical need” analysis (84 FR 7390).
• January 2025: an interim policy guidance on compounding with substances nominated for the list while their evaluation is pending.
• 2024–2025: docket comments. The notice records comments from October 2024 to June 2025 by the manufacturers of the approved products opposing the nominations, with citizen petitions on semaglutide and liraglutide, and responses from a trade association of outsourcing facilities.

Read together, the documents show the 2026 notice applying the 2019 two-question test to the three best-known GLP-1-type substances, with the FDA stating that it evaluates nominations “on a rolling basis” and intends to publish proposed and final determinations in groups until all sufficiently supported nominations have been decided.

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12. Primary Documents

1. U.S. Food and Drug Administration (2026). FDA Proposes to Exclude Semaglutide, Tirzepatide, and Liraglutide on 503B Bulks List. FDA News Release, 30 April 2026 — fda.gov press announcement
2. Food and Drug Administration, HHS (2026). List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act. Federal Register 91:23431–23444, 1 May 2026. FR Doc. 2026-08552. Docket No. FDA-2018-N-3240 — federalregister.gov 2026-08552
3. Food and Drug Administration, HHS (2026). List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act; Extension of Comment Period. Federal Register 91:38719–38720, 26 June 2026. FR Doc. 2026-12937. Docket No. FDA-2018-N-3240 — federalregister.gov 2026-12937
4. Public docket FDA-2018-N-3240 — regulations.gov FDA-2018-N-3240
5. U.S. Food and Drug Administration. 503B Bulk Drug Substances List (the agency’s page of evaluated substances) — fda.gov 503B bulks list

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Key Research Papers

1. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine 384(11):989-1002 — PubMed PMID: 33567185
2. Aroda VR, Aberle J, Bardtrum L, Christiansen E, Knop FK, Gabery S, Pedersen SD, Buse JB (2023). Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. Lancet 402(10403):693-704 — PubMed PMID: 37385279
3. Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, et al. (2023). Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 402(10403):705-719 — PubMed PMID: 37385278
4. Snitker S, Andersen A, Lindskov PS, van Marle S, Sode BF, Sparre T (2022). Comparison of the injection-site experience of semaglutide in a single-dose and a multidose pen-injector. Diabetes, Obesity and Metabolism 24(8):1643-1646 — PubMed PMID: 35434913
5. Pratap-Singh A, Guo Y, Baldelli A, Singh A (2023). Concept for a Unidirectional Release Mucoadhesive Buccal Tablet for Oral Delivery of Antidiabetic Peptide Drugs Such as Insulin, Glucagon-like Peptide 1 (GLP-1), and their Analogs. Pharmaceutics 15(9):2265 — PubMed PMID: 37765234
6. Aroda VR, Jørgensen NB, Kumar B, Lingvay I, Laulund AS, Buse JB (2025). High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial. Diabetes Care 48(6):905-913 — PubMed PMID: 40279144
7. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine 387(3):205-216 — PubMed PMID: 35658024
8. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. (2015). A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. New England Journal of Medicine 373(1):11-22 — PubMed PMID: 26132939

Papers 1–5 are in the reference list of the Federal Register notice (section V), and paper 6 is the published phase 2 trial the notice discusses in its semaglutide section. Papers 7 and 8 are the large weight-management trials of tirzepatide and liraglutide, added here as background on the substances; the notice does not cite them.

PubMed Topic Searches

1. PubMed: compounded semaglutide
2. PubMed: compounded tirzepatide
3. PubMed: outsourcing facilities and 503B compounding
4. PubMed: GLP-1 receptor agonist compounding safety

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Connections

• FDA and Regulation
• FDA Review of Compounded Peptides (2026)
• GLP-1 Receptor Agonists
• GLP-1 Receptor Agonists: Side Effects and Cautions
• GLP-1 Receptor Agonists: Weight Loss Studies
• GLP-1 Receptor Agonists: History and Origins
• Metformin, Berberine, and GLP-1 Agonists for Insulin Resistance
• Type 2 Diabetes
• Obesity
• Medicines and Oils

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