FDA Approves Tirzepatide, a Dual-Hormone Injection for Type 2 Diabetes (2022)

Table of Contents

1. What the FDA Approved on May 13, 2022
2. Two Gut Hormones: How the FDA Describes the Molecule
3. How the Medicine Is Used
4. The Clinical Trials Behind the Approval
5. What the Trials Found on Blood Sugar (HbA1c)
6. Side Effects and Warnings the FDA Lists
7. The Priority Review Voucher
8. From First Human Testing to Approval: The Review Dates
9. What the Approval Does Not Do
10. Dates and Legal Status as of October 18, 2026
11. How It Fits Later FDA Tirzepatide Actions
12. Primary Documents
13. Key Research Papers
14. Connections
15. Featured Videos

1. What the FDA Approved on May 13, 2022

The FDA’s Drug Trials Snapshot for the medicine gives its “Original Approval date” as May 13, 2022, and states that it is a drug that “improves blood sugar control in adults with type 2 diabetes mellitus (DM) when used in addition to diet and exercise.” The FDA’s list of Novel Drug Approvals for 2022 records the same date and the approved use as “To improve blood sugar control in diabetes, in addition to diet and exercise.”

The approval was of a new drug application (NDA), the application a company files asking the FDA to approve a new medicine for sale in the United States. A later Federal Register notice gives its number as NDA 215866 and states: “FDA has verified the applicant’s claim that NDA 215866 was approved on May 13, 2022.”

Tirzepatide was one of the FDA’s novel drugs of 2022. The FDA defines “novel” drugs as “new drugs never before approved or marketed in the U.S.,” and explains that “The active ingredient(s) in a novel drug has never been approved in the U.S.” Its list states that in 2022 the FDA’s drug center (the Center for Drug Evaluation and Research, CDER) “approved 37 novel drugs”; tirzepatide is entry 14 of the 37.

Blood sugar control in this approval is measured with HbA1c (hemoglobin A1c). The Snapshot calls it “a measure of blood sugar control” and states that in patients with type 2 diabetes, treatment with the medicine “can lower HbA1c.” The test itself is described on the site’s Hemoglobin A1C page.

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2. Two Gut Hormones: How the FDA Describes the Molecule

The FDA’s November 8, 2023 news release on the later weight-management approval of the same active ingredient describes how it acts: it “activates receptors of hormones secreted from the intestine (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)).” That is the sense in which this page calls it a “dual-hormone” injection: one molecule acts on the receptors for two different gut hormones.

The same 2023 release also states that the active ingredient was “already approved” under another trade name “to be used along with diet and exercise to help improve blood sugar (glucose) in adults” with type 2 diabetes, which is the 2022 approval this page reports.

The FDA documents read for this page do not describe the 2022 approval as the first of its kind, and this page makes no such claim. Medicines that act on the GLP-1 receptor alone are covered on the site’s GLP-1 Receptor Agonists page.

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3. How the Medicine Is Used

The Drug Trials Snapshot describes the approved product and its use:

• Form. “an injectable drug available in a prefilled pen.”
• Schedule and site. “It is injected once weekly under the skin (subcutaneously) of the abdomen, thigh, or upper arm.”
• Alone or with other medicines. It “may be used alone or in combination with other FDA-approved diabetes medications such as metformin, sulfonylureas, sodium-glucose co-transporter 2 inhibitors, and insulin.”
• With insulin. “In patients also using insulin injections,” the Snapshot states, the two “should be injected separately and not mixed into the same syringe.” That is the FDA’s instruction as written in the Snapshot.
• Doses studied. The trials described in the Snapshot tested three once-weekly doses: 5 mg, 10 mg and 15 mg.

The Snapshot itself carries a limitation: “Do not rely on Snapshots to make decisions regarding medical care,” and it points readers to the full prescribing information for “all the approved conditions of use.” Decisions about any diabetes medicine belong with a clinician.

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4. The Clinical Trials Behind the Approval

The Snapshot states that the FDA approved the medicine “based on evidence from nine clinical trials of 7,769 patients with type 2 diabetes mellitus, of which 5,415 of these patients received” it. The trials were run at 673 sites in 24 countries, including the United States.

• Efficacy (does it work). Five global, randomized trials with 6,263 adults with type 2 diabetes were used to judge how well the medicine worked. In each, the main measure (the “primary efficacy endpoint”) was the change in HbA1c from the start of the trial.
• Safety. All nine trials, 7,769 adults in total, were used to judge side effects. Four of the nine were safety-only trials; two of those were conducted in Japan.
• Two placebo-controlled trials. Patients were randomly assigned to the medicine or a placebo injection weekly, and “Neither the patient nor the healthcare provider knew which treatment was being given” (a double-blind design). Treatment lasted 40 weeks. In one, the medicine was used on its own; in the other, it was added to background insulin.
• Three trials against other diabetes medicines. The comparators were semaglutide 1 mg once weekly, insulin degludec and insulin glargine. These trials were open-label (patients and providers knew which medicine was given), used a non-inferiority design, and lasted 40 to 104 weeks.

A placebo, in the Snapshot’s glossary, is “An inactive substance or ‘sugar pill’ that looks the same as, and is given the same way as, an active drug.” A comparator is “A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.”

Who took part, according to the Snapshot’s demographics table for the five efficacy trials: 45% women and 55% men; 80% White, 8% American Indian or Alaska Native, 7% Asian and 4% Black or African American; 47% Hispanic or Latino; and 33% aged 65 or older.

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5. What the Trials Found on Blood Sugar (HbA1c)

The Snapshot’s Table 1, adapted from the FDA review, gives the “comparator-adjusted” change in HbA1c from baseline, that is, how much more HbA1c fell with tirzepatide than with the comparison treatment in the same trial. HbA1c is reported as a percentage, so a value of −1.7 means 1.7 percentage points lower. The figures for the 5 mg, 10 mg and 15 mg doses were:

• Against placebo, used alone (40 weeks): −1.7, −1.6 and −1.6.
• Against semaglutide 1 mg: −0.2, −0.4 and −0.5.
• Against insulin degludec: −0.6, −0.8 and −0.9.
• Against insulin glargine: −0.7, −0.9 and −1.0.
• Against placebo, added to background insulin (40 weeks): −1.2, −1.5 and −1.5.

On differences between groups of patients, the Snapshot reports that the medicine “worked similarly in females and males,” similarly across the racial groups analyzed (American Indian/Alaska Native, Asian, Black/African American and White), and similarly “in patients younger than 65 years of age and in patients that are 65 years and older.” It notes that some smaller racial subgroups were left out of individual trial analyses because of insufficient sample sizes.

The FDA pages read for this page report blood sugar results for the 2022 approval. Weight results from these trials are not given on those pages, and this page does not report them.

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6. Side Effects and Warnings the FDA Lists

The Snapshot lists these possible serious side effects: “inflammation of the pancreas (pancreatitis), low blood sugar, allergic reactions, kidney problems (kidney failure), severe stomach problems, and complications of diabetes-related eye disease (diabetic retinopathy).”

On thyroid tumors, it states: “In studies with rats,” the medicine “and medicines that work like” it “caused thyroid tumors, including thyroid cancer. It is not known if” it “will cause thyroid tumors, or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.” Thyroid cancer types are described on the site’s Thyroid Cancer page.

The most common side effects in the trials were “nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain.” The Snapshot’s Table 5, taken from the prescribing information, gives the share of patients in two placebo-controlled trials who reported each one at least once (placebo / 5 mg / 10 mg / 15 mg):

• Nausea: 4% / 12% / 15% / 18%
• Diarrhea: 9% / 12% / 13% / 17%
• Decreased appetite: 1% / 5% / 10% / 11%
• Vomiting: 2% / 5% / 5% / 9%
• Constipation: 1% / 6% / 6% / 7%
• Indigestion: 3% / 8% / 8% / 5%
• Abdominal pain: 4% / 6% / 5% / 5%

The Snapshot adds that, in those two trials, digestive side effects were reported by 46.8% of women and 34.4% of men on the medicine, against 25.7% and 15.6% on placebo, and that overall the occurrence of side effects “was similar” across sex, race and age groups. The site’s GLP-1 side effects page reports what the wider research describes for this family of medicines.

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7. The Priority Review Voucher

On August 29, 2022, the FDA published a notice in the Federal Register, the U.S. government’s daily publication of rules and official notices, announcing “the approval of a product redeeming a priority review voucher.” The notice states that “FDA has determined that the application for” tirzepatide injection, “approved May 13, 2022, meets the redemption criteria” (87 FR 52790; Docket No. FDA-2019-N-0895).

The voucher came from the FDA’s material threat medical countermeasure program. In the notice’s words, the Federal Food, Drug, and Cosmetic Act, “as amended by the 21st Century Cures Act, authorizes FDA to award priority review vouchers to sponsors of a material threat medical countermeasure application that meets certain criteria upon approval of such application.” The FDA “is required to publish notice of the issuance of priority review vouchers as well as the approval of products redeeming a priority review voucher,” which is why the 2022 notice exists. The notice cites section 565A of the Act for the program.

What priority review means is set out on the FDA’s patient page on the subject: “A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review).” The voucher notice does not say how the voucher affected this particular review.

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8. From First Human Testing to Approval: The Review Dates

On February 29, 2024, the FDA published its determination of the “regulatory review period” for tirzepatide injection (89 FR 14856; Docket No. FDA-2023-E-2112). The notice states that the FDA made the determination because an application had been submitted to the U.S. Patent and Trademark Office for the extension of a patent that claims the product. The dates it gives are:

• April 28, 2016: the date the investigational new drug application became effective. An investigational new drug application (IND) is the filing that allows a medicine that is not yet approved to be tested in people.
• September 15, 2021: the date the new drug application was submitted. The notice records that the applicant claimed September 14, 2021, but that “FDA records indicate that NDA 215866 was submitted on September 15, 2021.”
• May 13, 2022: the approval date.

The FDA determined that the regulatory review period was 2,208 days: 1,967 days in the testing phase and 241 days in the approval phase. The notice explains that “This determination of the regulatory review period establishes the maximum potential length of a patent extension”; the decision on the extension itself rests with the U.S. Patent and Trademark Office.

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9. What the Approval Does Not Do

• It is not a weight-loss approval. The 2022 approved use is blood sugar control in adults with type 2 diabetes, together with diet and exercise. Approval for chronic weight management came separately on November 8, 2023 (see section 11).
• It is not an approval for type 1 diabetes. The approved use names adults with type 2 diabetes only.
• It was not an approval for children. The 2022 use was for adults; a 2026 Federal Register notice reports that tirzepatide was approved on December 19, 2025, for pediatric patients 10 years of age and older.
• It is not an approval of any compounded tirzepatide. The approval covers the one product in NDA 215866; the story of compounded copies is told on the 2024 and 2026 pages linked in section 11.
• It does not settle the thyroid tumor question. The FDA Snapshot states that rat studies showed thyroid tumors and that it is not known whether the medicine causes them in people.
• It does not replace diet and exercise. The approved use is “in addition to diet and exercise.”

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10. Dates and Legal Status as of October 18, 2026

• April 28, 2016: the investigational new drug application takes effect.
• September 15, 2021: the new drug application (NDA 215866) is submitted.
• May 13, 2022: the FDA approves tirzepatide injection to improve blood sugar control in adults with type 2 diabetes.
• August 29, 2022: the FDA publishes notice that the application redeemed a material threat medical countermeasure priority review voucher (87 FR 52790).
• December 15, 2022: tirzepatide is first listed in shortage, as reported on the 2024 shortage page.
• November 8, 2023: the same active ingredient is approved, under another trade name, for chronic weight management.
• February 29, 2024: the FDA publishes its regulatory review period determination for patent extension (89 FR 14856).
• December 19, 2025: approval for pediatric patients 10 years and older, as stated in a May 1, 2026 FDA notice.
• May 1 and June 26, 2026: the FDA publishes, and then extends the comment period on, a notice that includes its proposal not to place semaglutide, tirzepatide or liraglutide on the list of bulk drug substances that outsourcing facilities may use in compounding (91 FR 23431; 91 FR 38719).

Status as of October 18, 2026: approval in effect. A check of the Federal Register through October 18, 2026 found no FDA document withdrawing or suspending the 2022 approval. The later documents found are the voucher notice, the patent-term notice, notices of product-specific guidances on the design of bioequivalence studies for abbreviated (generic) drug applications, and the 2026 compounding notices; none of them changes the 2022 approval.

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11. How It Fits Later FDA Tirzepatide Actions

The 2022 diabetes approval was the first FDA step for this active ingredient, and later actions built on it. Each is told on its own page:

• 2022–2024, shortage. Tirzepatide was first listed in shortage on December 15, 2022; the shortage, its end and what that meant for compounded copies are reported on FDA Ends the Tirzepatide Shortage, Limiting Compounded Copies (2024).
• November 8, 2023, weight management. The FDA approved the same active ingredient for chronic weight management in adults with obesity, or with overweight and at least one weight-related condition: FDA Approves Tirzepatide for Chronic Weight Management (2023).
• 2026, compounding list. The FDA’s proposal not to include semaglutide, tirzepatide or liraglutide on the list of bulk substances for outsourcing-facility compounding is reported on FDA Proposal on Compounded Semaglutide and Tirzepatide (2026).

A term recurs in those stories. Under section 503B of the Federal Food, Drug, and Cosmetic Act, outsourcing facilities may compound from “bulk drug substances (active pharmaceutical ingredients)” on a list for which the FDA finds “a clinical need,” in the words of the May 2026 notice.

Other FDA diabetes-related actions of 2022 are reported on their own pages, among them the November 2022 type 1 diabetes delay approval. The related semaglutide story is told on FDA Approves Semaglutide to Cut Heart Risk in Obesity (2024) and FDA Ends the Semaglutide Shortage and Compounded Copies (2025).

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12. Primary Documents

1. U.S. Food and Drug Administration. Drug Trials Snapshot for tirzepatide injection (type 2 diabetes), original approval May 13, 2022. Content current as of June 13, 2023. Listed among the FDA’s Drug Trials Snapshots on fda.gov; its web address carries the product’s brand name, so it is given here as plain text without a link.
2. U.S. Food and Drug Administration. Novel Drug Approvals for 2022 (entry 14, tirzepatide, 5/13/2022). Content current as of January 2, 2025 — fda.gov Novel Drug Approvals for 2022
3. Food and Drug Administration, HHS (2022). Notice of Approval of Product Under Voucher: Material Threat Medical Countermeasure Priority Review Voucher. Notice. Federal Register 87 FR 52790, August 29, 2022. Docket No. FDA-2019-N-0895 — FR Doc. 2022-18523
4. Food and Drug Administration, HHS (2024). Determination of Regulatory Review Period for Purposes of Patent Extension (tirzepatide injection; the published title carries the brand name). Notice. Federal Register 89 FR 14856, February 29, 2024. Docket No. FDA-2023-E-2112 — FR Doc. 2024-04157
5. U.S. Food and Drug Administration (2023). FDA Approves New Medication for Chronic Weight Management. FDA News Release, November 8, 2023 (cited here for the FDA’s description of how the molecule acts) — fda.gov news release
6. U.S. Food and Drug Administration. Priority Review. Patient information page — fda.gov Priority Review page
7. 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. Notice. Federal Register 91 FR 23431, May 1, 2026 — FR Doc. 2026-08552
8. 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 FR 38719, June 26, 2026 — FR Doc. 2026-12937

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Key Research Papers

1. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D’Alessio DA, Haupt A (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Molecular Metabolism 18:3-14 — PubMed PMID: 30473097
2. Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A (2018). Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet 392(10160):2180-2193 — PubMed PMID: 30293770
3. Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet 398(10295):143-155 — PubMed PMID: 34186022
4. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine 385(6):503-515 — PubMed PMID: 34170647
5. Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, Bray R, Rodríguez Á (2021). Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet 398(10300):583-598 — PubMed PMID: 34370970
6. Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ (2021). Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet 398(10313):1811-1824 — PubMed PMID: 34672967
7. Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á (2022). Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA 327(6):534-545 — PubMed PMID: 35133415

The first paper describes the discovery of the molecule (then known by a laboratory code) and its early testing, and the second reports its phase 2 trial in type 2 diabetes. The last five are the published reports of phase 3 trials against placebo, semaglutide, insulin degludec, insulin glargine and placebo added to insulin glargine, the comparisons summarized in section 5.

PubMed Topic Searches

1. PubMed: tirzepatide and type 2 diabetes
2. PubMed: dual GIP and GLP-1 receptor agonists
3. PubMed: tirzepatide safety and adverse events

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Connections

• FDA Actions of 2022
• FDA and Regulation
• Type 2 Diabetes
• Diabetes
• Obesity
• GLP-1 Receptor Agonists
• GLP-1 Side Effects and Cautions
• Hemoglobin A1C
• Pancreatitis
• Diabetic Retinopathy
• Tirzepatide for Weight Management (2023)
• Tirzepatide Shortage Ends (2024)
• Compounded GLP-1 Proposal (2026)
• Semaglutide Heart-Risk Approval (2024)
• Teplizumab for Type 1 Diabetes Delay (2022)
• Buprenorphine Dental Problems Warning (2022)
• ALS Drug Approval, Later Withdrawn (2022)

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