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GLP-1 receptor agonists and ileus, from the label record

By Kelsey research · Published

Glucagon-like peptide-1 (GLP-1) receptor agonists are injected or oral medicines used for type 2 diabetes and weight management. Below is when the FDA-approved labels of semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda) and dulaglutide (Trulicity) added ileus (a blockage of normal bowel movement) and intestinal obstruction, from Drugs@FDA approval histories, the approved labels and FDA's supplement approval letters. Other products are not covered. For dulaglutide, only the 2022 addition is traced here; the table records no 2025 obstruction update for Trulicity.

For each term, the table gives the first label version on Drugs@FDA that contains it. Drugs@FDA does not necessarily show every label version, so an earlier version could exist outside it.

Chronology, June 2022 to October 2025

Date Event Date type Source
Jun 15, 2022 FDA identifies a "Newly Identified Safety Signal" for the risk of intestinal obstruction, as stated in its 2023 Victoza approval letter. stated in fda letter [1]
Jul 15, 2022 Novo Nordisk files the Rybelsus supplement S-012. submitted [2]
Nov 8, 2022 FDA's Division of Pharmacovigilance completes a review of GLP-1 receptor agonists and intestinal obstruction, which FDA's 2025 labeling review cites by date. stated in fda review [3]
Nov 17, 2022 Trulicity label (SUPPL-51) lists "Gastrointestinal: ileus" among postmarketing reactions. The letter describes the supplement as a pediatric indication. approved [4][5]
Dec 23, 2022 Wegovy label (SUPPL-5) lists ileus under postmarketing reactions. The letter describes the supplement as a pediatric indication and does not mention ileus. approved [6][7]
Jan 12, 2023 Rybelsus S-012 approved. The letter lists "adding 'Gastrointestinal: ileus' to section 6.2." approved [2][8]
Mar 22, 2023 Novo Nordisk files the Saxenda supplement S-016, to add ileus to postmarketing experience. submitted [9]
Mar 23 and 24, 2023 Novo Nordisk files Ozempic supplements S-020 and S-021. submitted [10]
Apr 20, 2023 Saxenda S-016 approved. approved [9]
Jul 5, 2023 Victoza S-039 approved. The letter says ileus was added "to align with other glucagon-like peptide (GLP) 1 products based on a Newly Identified Safety Signal." approved [1]
Sep 22, 2023 Ozempic S-021 approved, adding "Gastrointestinal: Ileus" to section 6.3, Postmarketing Experience. approved [10]
Sep 6, 2024 FDA notifies sponsors under section 505(o)(4) of new safety information for GLP-1 receptor agonist labels, on pulmonary aspiration during anesthesia or deep sedation. This is a separate risk. stated in fda letter [11]
Nov 1, 2024 Ozempic S-032 approved with the aspiration language. approved [11]
Dec 12, 2024 The JPML orders a further action transferred to MDL No. 3094, a centralized proceeding for GLP-1 receptor agonist actions in the Eastern District of Pennsylvania. published [12]
Mar 21, 2025 Novo Nordisk files Ozempic S-035, Wegovy S-026 and Rybelsus S-028. submitted [13][14][15]
Mar 28, 2025 FDA emails Novo Nordisk asking for the same supplement for its liraglutide products, as FDA's 2025 labeling review records. stated in fda review [3]
Apr 14, 2025 Novo Nordisk files Victoza S-046 and Saxenda S-022, adding intestinal obstruction and severe constipation including fecal impaction to postmarketing experience. submitted [16][17]
Oct 14, 2025 Ozempic S-035, Wegovy S-026, Victoza S-046 and Saxenda S-022 approved. approved [13][14][16][17]
Oct 17, 2025 Rybelsus S-028 approved. approved [15]

October 2025 adds intestinal obstruction and a sentence on GLP-1 receptor agonists

The five October 2025 letters describe similar revisions. Each adds "intestinal obstruction, severe constipation including fecal impaction" to the postmarketing section. Ozempic, Wegovy, Rybelsus, Victoza and Saxenda each also add, in the Warnings and Precautions section on severe gastrointestinal adverse reactions, the sentence "Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists." The Ozempic letter also adds acute kidney injury and, in a second supplement, headache. The Saxenda letter adds headache and replaces "acute renal failure or worsening of chronic renal failure" with "acute kidney injury".[13][14][15][16][17]

Ileus sits in Postmarketing Experience

In each label above, ileus appears in the postmarketing experience subsection. The Ozempic label that first added ileus says its postmarketing reactions are "reported voluntarily from a population of uncertain size," so that "it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure."[10] The October 2025 Ozempic label keeps ileus in that subsection and adds a general statement about severe gastrointestinal adverse reactions to the warnings.[13]

What the record shows, and what it leaves open

Ileus entered several GLP-1 receptor agonist labels within about ten months. The Trulicity, Wegovy and Rybelsus labels did so between November 2022 and January 2023, Saxenda in April 2023, Victoza in July 2023 and Ozempic in September 2023. The Victoza letter ties its addition to a signal FDA identified on June 15, 2022, and to alignment with other products in the class. The Saxenda S-016, Ozempic and Rybelsus letters state what was added but give no reason. The Wegovy and Trulicity letters describe other changes, so the ileus entries in those labels can be seen only by comparing label versions.

A second step came in 2025. Obstruction and severe constipation were added, and the warnings gained a sentence about GLP-1 receptor agonists. The letters say these were revisions the sponsor proposed in supplements dated March 21, 2025 (semaglutide products) and April 14, 2025 (liraglutide products), approved on October 14 and 17, 2025.

The record does not show the underlying data. The letters do not say how many reports FDA reviewed, or which database or study supported the June 2022 signal. FDA's Ozempic history now links review packages for supplements S-032, S-035 and S-037. This page read the S-035 package, whose labeling review says FDA's pharmacovigilance office updated its November 2022 review, added fecal impaction and severe constipation to its FAERS search, and that a review filed on October 14, 2025 addressed the signal for the whole class.[3] The passages that would give case counts and results are redacted or not legible in the PDF, so the data themselves are still not shown. The S-032 package concerns pulmonary aspiration, a separate risk, and was not used for ileus. This page did not locate review documents for the Wegovy, Rybelsus, Victoza and Saxenda supplements. The label sections it cites are postmarketing lists, which by their own terms do not establish frequency or causation.

It also does not show whether any individual's condition was caused by a drug. The MDL entry above shows only that a centralized proceeding exists. This page takes no position on the claims in it.

Sources

  1. FDA, Victoza supplement approval letter, NDA 022341/S-039 (sNDA dated January 6, 2023), approved July 5, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/022341Orig1s039ltr.pdf
  2. FDA, Drugs@FDA, Rybelsus NDA 213051, approval history. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213051
  3. FDA, approval package for Ozempic NDA 209637/S-035, labeling review of the "intestinal obstruction" supplements (approval date October 14, 2025). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2026/209637Orig1s035.pdf
  4. FDA, Drugs@FDA, Trulicity BLA 125469, approval history. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125469
  5. FDA, Trulicity label, SUPPL-51, revised 11/2022 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125469s051lbl.pdf) and approval letter (https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/125469Orig1s051ltr.pdf).
  6. FDA, Drugs@FDA, Wegovy NDA 215256, approval history. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215256
  7. FDA, Wegovy label, SUPPL-5, revised 12/2022 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215256s005lbl.pdf) and approval letter (https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/215256Orig1s005ltr.pdf).
  8. FDA, Rybelsus supplement approval letter, NDA 213051/S-012 (sNDA dated July 15, 2022). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/213051Orig1s012ltr.pdf
  9. FDA, Saxenda supplement approval letter, NDA 206321/S-016 (sNDA dated March 22, 2023), and Drugs@FDA approval history (04/20/2023). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/206321Orig1s016ltr.pdf and https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=206321
  10. FDA, Ozempic supplement approval letter, NDA 209637/S-020 and S-021 (sNDAs dated and received March 23 and 24, 2023), and label revised 9/2023. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/209637Orig1s020,s021ltr.pdf and https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209637s020s021lbl.pdf
  11. FDA, Ozempic supplement approval letter, NDA 209637/S-032 (sNDA dated October 4, 2024; refers to FDA's September 6, 2024 letter under section 505(o)(4)), and Drugs@FDA approval history. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/209637Orig1s032ltr.pdf and https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209637
  12. Judicial Panel on Multidistrict Litigation, Transfer Order, In re Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) Products Liability Litigation, MDL No. 3094, Document 272, filed 12/12/24. https://www.jpml.uscourts.gov/sites/jpml/files/MDL-3094-Transfer_Order-12-24.pdf
  13. FDA, Ozempic supplement approval letter, NDA 209637/S-035 and S-037 (S-035 dated March 21, 2025), and label revised 10/2025; approval date 10/14/2025 per Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/209637Orig1s035,s037ltr.pdf and https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209637s035,209637s037lbl.pdf
  14. FDA, Wegovy supplement approval letter, NDA 215256/S-026 (sNDA dated March 21, 2025), approved 10/14/2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215256Orig1s026ltr.pdf
  15. FDA, Rybelsus supplement approval letter, NDA 213051/S-024, S-028 and S-029 (S-028 dated March 21, 2025), approved 10/17/2025 per Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/213051Orig1s024,s028,s029ltr.pdf
  16. FDA, Victoza supplement approval letter, NDA 022341/S-046 (sNDA dated and received April 14, 2025), signed October 14, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/022341Orig1s046ltr.pdf
  17. FDA, Saxenda supplement approval letter, NDA 206321/S-022 (sNDA dated and received April 14, 2025), signed October 14, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/206321Orig1s022ltr.pdf