The Complete FDA Approval History of Tirzepatide (Mounjaro and Zepbound)

If you have tried to pin down when tirzepatide was approved, you have probably run into the same wall everyone does: the answer depends on which brand name you mean, and there are two of them. Mounjaro and Zepbound contain exactly the same drug at exactly the same strengths, made by the same company, but they went through the FDA as two separate applications with two separate sets of indications.

This page lays out every US approval decision on tirzepatide in date order, with the application and supplement numbers so you can check any of it yourself. It is a record of what regulators decided, not medical advice. Whether any of these medicines makes sense for a particular person is a conversation for a healthcare provider.

What is tirzepatide and why does it have two brand names?

Tirzepatide is a once-weekly injection that activates two gut hormone receptors at once: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). Most of the other drugs people group under the GLP-1 umbrella, including semaglutide, hit only the GLP-1 receptor. Tirzepatide hitting both is what earns it the “dual agonist” label.

Eli Lilly took tirzepatide to the FDA first as a diabetes drug. That became Mounjaro, approved under new drug application NDA 215866. When the company later sought approval for weight management, it did not file a supplement to the existing Mounjaro application. It filed a whole new application, NDA 217806, which the FDA classifies internally as a “Type 10 - New Indication Submitted as Distinct NDA - Not Consolidated” [4]. That new application became Zepbound.

That choice has real consequences for patients. Two applications mean two labels, two sets of approved uses, two prices, and two different insurance coverage stories. It is also why a supplement approved for one brand often has a mirror-image twin approved for the other on the same day.

When did the FDA approve Mounjaro?

May 13, 2022. The approval letter shows Lilly filed the application on September 14, 2021, with FDA recording receipt the next day, so the review ran just under eight months [1]. The approved use was narrow: as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

The original label carried a boxed warning about thyroid C-cell tumors observed in rodents, a warning that has stayed on both tirzepatide labels ever since [2]. The approval letter also imposed two postmarketing requirements that shaped the next four years of the drug’s regulatory life:

• PMR 4271-1 required a randomized, placebo-controlled study in children aged 10 to 17 with type 2 diabetes.
• PMR 4272-2 required a study measuring tirzepatide concentrations in human breast milk [1].

Both were eventually completed, and both produced label changes that appear later in this timeline.

What happened between the two approvals?

In October 2022, five months after the Mounjaro approval, the FDA granted tirzepatide Fast Track designation for obesity and overweight with weight-related comorbidities. Fast Track means more frequent meetings with the agency and the ability to submit parts of an application as they are ready. It does not lower the bar for evidence.

In July 2023, the FDA approved supplements S-002 and S-006 to the Mounjaro application, adding single-dose vial presentations in all six strengths [5]. This is a piece of trivia that turned out to matter enormously later: Lilly never marketed those Mounjaro vials in the United States, and the FDA would later point out that they were consequently never on the drug shortage list.

When was Zepbound approved?

November 8, 2023. The approval letter describes the indication as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of 30 or greater, or 27 or greater in the presence of at least one weight-related condition such as high blood pressure, high cholesterol, type 2 diabetes, obstructive sleep apnea or cardiovascular disease [7].

The approval rested on the SURMOUNT-1 and SURMOUNT-2 trials, both 72-week randomized studies against placebo.

Worth noting for anyone reading British or European coverage: the same day the FDA created Zepbound, the UK’s MHRA simply added weight management to the existing Mounjaro license. In the UK and across the EU there is no Zepbound brand at all.

What did the FDA add to the labels in 2024?

2024 was a heavy year for tirzepatide labeling, driven largely by class-wide safety work rather than new indications.

March 28, 2024 — Zepbound supplement S-003 added a single-dose vial container closure system [4]. That approval is what made Lilly’s later self-pay vial offering possible.

September 6, 2024 — The FDA sent Lilly a letter under section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act, a provision that lets the agency compel labeling changes for new safety information. The subject was the serious risk of pulmonary aspiration in patients undergoing surgery or procedures requiring general anesthesia or deep sedation [6].

October 18, 2024 — Five Zepbound supplements were approved together. S-006 added data from SURMOUNT-3 (tirzepatide started after an intensive lifestyle program) and SURMOUNT-4 (maintenance of weight loss). S-005 retitled the gastrointestinal warning to “Severe Gastrointestinal Adverse Reactions” and added dysgeusia, a distorted sense of taste. S-011 added dysesthesia, an abnormal skin sensation. S-015 tidied the indication statement and removed a Patient Selection subsection [8].

November 1, 2024 — Three Mounjaro supplements landed on the same day. S-010 updated the severe gastrointestinal language and added dysgeusia, S-015 added dysesthesia, and S-022 implemented the September aspiration letter [6].

When was Zepbound approved for sleep apnea?

December 20, 2024, and it was a genuine first. No drug had ever been approved to treat obstructive sleep apnea before. The FDA’s own announcement quoted Sally Seymour, director of the Division of Pulmonology, Allergy and Critical Care, calling it “the first drug treatment option for certain patients with obstructive sleep apnea” [9].

The approval was based on two 52-week randomized, double-blind, placebo-controlled studies run under a single master protocol registered as NCT05412004 and known as SURMOUNT-OSA [22]. Together they enrolled 469 adults with obesity and moderate-to-severe sleep apnea who did not have type 2 diabetes. One study enrolled people using positive airway pressure, the standard therapy; the other enrolled people unable or unwilling to use it. The main measure was change in the apnea-hypopnea index at week 52, which counts breathing interruptions per hour of sleep [9].

The FDA noted in its announcement that the improvement in apnea-hypopnea index is likely related to the weight reduction the drug produces. Zepbound carried Fast Track, Priority Review and Breakthrough Therapy designations for this indication [9].

That single approval also unlocked a coverage door. Medicare Part D generally cannot cover a drug used for weight loss, but it can cover an obesity drug used for a separate FDA-approved purpose. Within weeks, CMS confirmed that existing Part D rules let plans cover Zepbound for sleep apnea.

That is no longer the only Medicare route. On July 1, 2026 CMS opened the Medicare GLP-1 Bridge, a time-limited demonstration running through December 31, 2027 that lets eligible Part D enrollees get certain weight-loss medicines for a flat $50 a month. For tirzepatide, the Bridge covers the Zepbound KwikPen only; the single-dose Zepbound pen and the Zepbound vials are not covered [24]. Eligibility and enrollment rules are set by CMS, not by this page.

What changed on the labels in 2025?

February 7, 2025 — Zepbound supplement S-020 added labeling for single-dose vials in a four-pack, essentially a month in one carton [4].

May 1, 2025 — Lilly told investors it had withdrawn its US application for heart failure with preserved ejection fraction. The Phase 3 SUMMIT trial had met both primary endpoints, but according to Lilly’s chief scientific officer the FDA indicated an additional confirmatory clinical trial would be required. Reviews continued in other countries [16]. As of September 14, 2026 there is still no US heart failure indication for tirzepatide.

May 28, 2025 — Mounjaro supplement S-031 added alopecia, meaning hair loss, to the Postmarketing Experience section, in response to an FDA supplement request letter dated February 3, 2025. The same supplement removed two Limitations of Use from the front of the label: the statement that Mounjaro is not indicated in type 1 diabetes, and the statement that it has not been studied in patients with a history of pancreatitis [11].

September 9, 2025 — The FDA’s drug center sent Eli Lilly’s chief executive a warning letter about a direct-to-consumer video, the March 2024 program “An Oprah Special: Shame, Blame, and the Weight Loss Revolution.” The agency concluded the video was false or misleading, that it minimized serious risks including the boxed warning, that it featured two paid Lilly consultants and a Lilly vice president, and that it was never submitted to the FDA at the time of first dissemination as regulations require. The letter also noted the FDA had given Lilly similar advisory comments back in June 2022 [19].

September 25, 2025 — Matching supplements on both applications revised the Lactation subsection of the labels, based on a milk-only study that satisfied postmarketing requirement 4272-2 from the original 2022 approval [12].

December 19, 2025 — Mounjaro supplement S-039 expanded the indication to pediatric patients aged 10 and older with type 2 diabetes, based on the SURPASS-PEDS trial (NCT05260021). The FDA letter states plainly that this closed postmarketing requirement 4271-1 and that the supplement carried pediatric information under both the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act [13][23]. Zepbound remains adult-only.

What changed in 2026?

January 7, 2026 — Parallel supplements on both applications added a multiple-dose single-patient-use vial presentation [3][4].

January 20, 2026 — The FDA approved the Mounjaro KwikPen and Zepbound KwikPen, six presentations each holding four fixed-volume weekly doses. The approval letter tells a slow story: the supplement was submitted on September 28, 2023, drew an FDA action letter on January 29, 2025, and was only approved after Lilly filed a complete response on December 2, 2025 [14]. That is a more than two-year path for what is essentially a device change. Europe had approved the equivalent multi-dose pen back in April 2024.

February 25, 2026 — Zepbound supplement S-042 carried two significant safety changes at once. First, in response to an FDA notification of a newly identified safety signal dated April 28, 2025 and a supplement request letter dated October 14, 2025, the label added intestinal obstruction and severe constipation including fecal impaction to Postmarketing Experience. Second, following a separate FDA request dated January 13, 2026, the label removed subsection 5.9, Suicidal Ideation and Behavior, entirely [15]. That removal closed a review the agency had opened in July 2023.

April 22, 2026 — A joint supplement across both applications accepted stability data showing single-dose tirzepatide presentations hold up for 21 days of in-use storage, including repeated cycling between refrigerated conditions and room temperature up to 30 degrees Celsius [3].

August 26 and 27, 2026 — The biggest label expansion since the sleep apnea approval. Supplement S-044 gave Mounjaro a new indication: reducing the risk of major adverse cardiovascular events, meaning cardiovascular death, non-fatal heart attack or non-fatal stroke, in adults with type 2 diabetes at high risk for those events [17]. The same letter approved S-045, which lets the 2.5 mg dose be used for ongoing glycemic control rather than only as a starting dose, and revised the Diabetic Retinopathy Complications warning on the basis of SURPASS-CVOT [17]. Zepbound supplement S-041, an efficacy supplement approved the day before on August 26, 2026, carried the same trial data across to the weight-management application [4].

The basis was SURPASS-CVOT (NCT04255433), which Lilly describes as the first cardiovascular outcomes trial to compare two incretin medicines head-to-head rather than against placebo. It randomized 13,299 people with type 2 diabetes and established atherosclerotic cardiovascular disease across 640 sites in 30 countries. The trial ran about five years, with a median follow-up of roughly four years. Tirzepatide was non-inferior to dulaglutide, with a hazard ratio of 0.92 and a 95.3 percent confidence interval of 0.83 to 1.01, an 8 percent lower rate of major adverse cardiovascular events. Full results were published in the New England Journal of Medicine [18][21][25].

That result deserves a plain-English gloss. Non-inferiority means tirzepatide was shown not to be meaningfully worse than a comparator that already has proven cardiovascular benefit. Lilly’s own release states explicitly that superiority to dulaglutide was not established [18].

What has tirzepatide not been approved for in the US?

As of September 14, 2026, the FDA has not approved tirzepatide for:

• Heart failure with preserved ejection fraction, after Lilly withdrew the application in May 2025 [16]
• Chronic kidney disease
• Metabolic dysfunction-associated steatohepatitis
• Weight management in children or adolescents
• Type 1 diabetes

There is also no approved generic tirzepatide, and two separate things stand in the way of one. The first is statutory exclusivity: the Fifth Circuit noted in August 2026 that because tirzepatide was a new active moiety, Lilly’s right to be the only manufacturer of tirzepatide products “extends to 2027” [26]. The second is patents. Compilations of the Orange Book listings show composition and method-of-use patents with expiry dates in 2039, though those dates can shift through litigation, settlements and patent term adjustments, and this site has not read the Orange Book entries directly [20].

How can I check any of this myself?

Everything above comes from documents anyone can read for free.

• Drugs@FDA lists every approved supplement on both applications, with links to the approval letter and the label as approved. Search NDA 215866 for Mounjaro and NDA 217806 for Zepbound.
• Approval letters are short, usually two to six pages, and the second paragraph almost always says exactly what the supplement did.
• ClinicalTrials.gov holds the registration record for every trial named in this article.
• FDA press announcements cover the headline approvals, such as the sleep apnea decision.

If a website gives you a tirzepatide approval date with no supplement number and no link to an FDA letter, treat it as unverified until you can match it to one of these sources.

Sources

1. Mounjaro NDA approval letter, May 13, 2022 — FDA
2. Mounjaro prescribing information as approved, 2022 — FDA
3. Drugs@FDA record, NDA 215866 — FDA openFDA API
4. Drugs@FDA record, NDA 217806 — FDA openFDA API
5. Mounjaro supplement approval letter, S-002 and S-006 — FDA
6. Mounjaro supplement approval letter, S-010, S-015 and S-022 — FDA
7. Zepbound NDA approval letter, November 8, 2023 — FDA
8. Zepbound supplement approval letter, S-005 through S-019 — FDA
9. FDA Approves First Medication for Obstructive Sleep Apnea — FDA
10. Zepbound supplement approval letter, S-013 — FDA
11. Mounjaro supplement approval letter, S-031 — FDA
12. Mounjaro supplement approval letter, S-034 — FDA
13. Mounjaro supplement approval letter, S-039 pediatric — FDA
14. Mounjaro KwikPen supplement approval letter, S-009 — FDA
15. Zepbound supplement approval letter, S-042 — FDA
16. Lilly Withdraws Tirzepatide Application to FDA for Heart Failure — ConscienHealth
17. Mounjaro supplement approval letter, S-044 and S-045 — FDA
18. FDA approves Lilly’s Mounjaro to reduce cardiovascular risk — Eli Lilly and Company
19. Warning Letter to Eli Lilly and Company, September 9, 2025 — FDA
20. Generic Zepbound Availability and patent listing — Drugs.com
21. SURPASS-CVOT, NCT04255433 — ClinicalTrials.gov
22. SURMOUNT-OSA, NCT05412004 — ClinicalTrials.gov
23. SURPASS-PEDS, NCT05260021 — ClinicalTrials.gov
24. Medicare GLP-1 Bridge: GLP-1 Drugs for $50 a Month, fact sheet CMS Product No. 12234 — Medicare.gov
25. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-2420
26. Outsourcing Facilities Association v. FDA, No. 25-10600, slip op. at 3 (5th Cir. Aug. 27, 2026) — US Court of Appeals for the Fifth Circuit