Tirzepatide Explained

Width:300
Pronounce:
Tradename:Mounjaro, Zepbound
Dailymedid:Tirzepatide
Pregnancy Au:D
Routes Of Administration:Subcutaneous
Class:Antidiabetic, GLP-1 receptor agonist
Atc Prefix:A10
Atc Suffix:BX16
Legal Au:S4
Legal Au Comment:[1] [2] [3]
Legal Ca:Rx-only
Legal Ca Comment:[4] [5] [6]
Legal Uk:POM
Legal Uk Comment:[7] [8]
Legal Us:Rx-only
Legal Us Comment:[9] [10]
Legal Eu:Rx-only
Legal Eu Comment:[11]
Bioavailability:80%
Protein Bound:Albumin
Metabolism:Proteolytic cleavage, β-oxidation of fatty diacid section and amide hydrolysis
Elimination Half-Life:5 days
Excretion:Urine and faeces
Cas Number:2023788-19-2
Pubchem:156588324
Iuphar Ligand:11429
Drugbank:DB15171
Chemspiderid:76714503
Unii:OYN3CCI6QE
Kegg:D11360
Chebi:194186
Chembl:4297839
Synonyms:LY3298176, GIP/GLP-1 RA
Iupac Name:(2S)-2-20-(5S)-6-(2S,3S)-1-(2S)-1-(2S)-5-amino-1-(2S)-6-amino-1-(2S)-1-(2S)-1-(2S)-1-(2S)-5-amino-1-(2S)-1-(2S)-1-(2S,3S)-1-(2S)-1-2-2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethylamino]-2-oxoethylamino]-1-oxopropan-2-ylamino]-3-methyl-1-oxopentan-2-ylamino]-4-methyl-1-oxopentan-2-ylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-ylamino]-1,5-dioxopentan-2-ylamino]-3-methyl-1-oxobutan-2-ylamino]-1-oxo-3-phenylpropan-2-ylamino]-1-oxopropan-2-ylamino]-1-oxohexan-2-ylamino]-1,5-dioxopentan-2-ylamino]-1-oxopropan-2-ylamino]-3-methyl-1-oxopentan-2-ylamino]-5-(2S)-2-(2S)-2-2-(2S,3S)-2-(2S)-2-(2S)-2-(2S)-2-(2S)-2-(2S,3R)-2-(2S)-2-(2S,3R)-2-2-(2S)-2-2-(2S)-2-amino-3-(4-hydroxyphenyl)propanoylamino]-2-methylpropanoylamino]-4-carboxybutanoylamino]acetylamino]-3-hydroxybutanoylamino]-3-phenylpropanoylamino]-3-hydroxybutanoylamino]-3-hydroxypropanoylamino]-3-carboxypropanoylamino]-3-(4-hydroxyphenyl)propanoylamino]-3-hydroxypropanoylamino]-3-methylpentanoylamino]-2-methylpropanoylamino]-4-methylpentanoylamino]-3-carboxypropanoylamino]-6-oxohexylamino]-20-oxoicosanoylamino]-5-[2-[2-[2-[2-[2-(carboxymethoxy)ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-5-oxopentanoic acid| C=225 | H=348 | N=48 | O=68| SMILES = C[C@@H](O)[C@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)CC1C=CC(O)=CC=1)C(=O)N[C@@H](CC1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NC(C)(C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCCCC(O)=O)C(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2C=CC=CC1=2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O| StdInChI = 1S/C225H348N48O68/c1-23-126(10)183(264-198(311)146(64-50-52-88-226)246-202(315)157(109-180(297)298)252-199(312)152(103-124(6)7)261-223(337)225(21,22)269-217(330)185(128(12)25-3)266-209(322)163(120-278)257-200(313)153(107-138-74-78-141(282)79-75-138)250-203(316)158(110-181(299)300)253-207(320)162(119-277)259-216(329)187(134(18)280)267-206(319)155(106-136-60-44-41-45-61-136)254-215(328)186(133(17)279)262-174(289)114-237-193(306)147(83-87-179(295)296)260-222(336)224(19,20)268-192(305)143(227)104-137-72-76-140(281)77-73-137)214(327)242-131(15)190(303)244-148(80-84-168(228)283)196(309)245-145(65-51-53-89-231-175(290)121-340-100-99-339-97-91-233-176(291)122-341-101-98-338-96-90-232-170(285)86-82-150(221(334)335)243-171(286)70-46-38-36-34-32-30-28-26-27-29-31-33-35-37-39-47-71-178(293)294)195(308)240-130(14)191(304)248-154(105-135-58-42-40-43-59-135)205(318)263-182(125(8)9)212(325)247-149(81-85-169(229)284)197(310)251-156(108-139-111-234-144-63-49-48-62-142(139)144)201(314)249-151(102-123(4)5)204(317)265-184(127(11)24-2)213(326)241-129(13)189(302)236-112-172(287)235-115-177(292)270-92-54-66-164(270)210(323)258-161(118-276)208(321)256-160(117-275)194(307)238-113-173(288)239-132(16)218(331)272-94-56-68-166(272)220(333)273-95-57-69-167(273)219(332)271-93-55-67-165(271)211(324)255-159(116-274)188(230)301/h40-45,48-49,58-63,72-79,111,123-134,143,145-167,182-187,234,274-282H,23-39,46-47,50-57,64-71,80-110,112-122,226-227H2,1-22H3,(H2,228,283)(H2,229,284)(H2,230,301)(H,231,290)(H,232,285)(H,233,291)(H,235,287)(H,236,302)(H,237,306)(H,238,307)(H,239,288)(H,240,308)(H,241,326)(H,242,327)(H,243,286)(H,244,303)(H,245,309)(H,246,315)(H,247,325)(H,248,304)(H,249,314)(H,250,316)(H,251,310)(H,252,312)(H,253,320)(H,254,328)(H,255,324)(H,256,321)(H,257,313)(H,258,323)(H,259,329)(H,260,336)(H,261,337)(H,262,289)(H,263,318)(H,264,311)(H,265,317)(H,266,322)(H,267,319)(H,268,305)(H,269,330)(H,293,294)(H,295,296)(H,297,298)(H,299,300)(H,334,335)/t126-,127-,128-,129-,130-,131-,132-,133+,134+,143-,145-,146-,147-,148-,149-,150+,151-,152-,153-,154-,155-,156-,157-,158-,159-,160-,161-,162-,163-,164-,165-,166-,167-,182-,183-,184-,185-,186-,187-/m0/s1| StdInChI_comment = | StdInChIKey = BTSOGEDATSQOAF-SMAAHMJQSA-N| density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

Tirzepatide is an antidiabetic medication used for the treatment of type2 diabetes[12] [13] and for weight loss. Tirzepatide is administered via subcutaneous injections (under the skin). It is sold under the brand names Mounjaro for diabetes treatment, and Zepbound for weight loss.

Tirzepatide is a GIP receptor and glucagon-like peptide-1 agonist. The most common side effects include nausea, vomiting, diarrhea, decreased appetite, constipation, upper abdominal discomfort, and abdominal pain.[14]

Tirzepatide was approved for treatment of diabetes in the United States in May 2022, in the European Union in September 2022, in Canada in November 2022,[15] and in Australia in December 2022. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[16] [17] It was approved by the FDA for weight loss in November 2023.[18] In November 2023, the UK Medicines and Healthcare products Regulatory Agency revised the indication for tirzepatide to include treatment for weight loss.[19]

In April 2024, the Food and Drug Administration’s drug shortage database indicates most doses of Zepbound and Mounjaro will be in short supply through the second quarter 2024.[20]

Medical uses

Tirzepatide is indicated to improve blood-sugar control in adults with type2 diabetes, as an addition to diet and exercise.

Tirzepatide is also indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management.[21]

Tirzepatide has demonstrated significant benefits in obese patients with a common type of heart failure, preserved ejection fraction (HFpEF) in a Phase 3 trial.[22] [23] Over two years, Tirzepatide reduced the risk of major complications, including urgent heart failure visits, hospitalizations, increased diuretic treatment, and cardiovascular-related deaths, by 38% compared to placebo.[24] This makes Tirzepatide the second GLP-1 drug to show positive results in this area, following semaglutide to date.

Contraindications

Tirzepatide is contraindicated for use in people with a personal or family history of medullary thyroid cancer or for use in people with multiple endocrine neoplasia syndrome type2.

Adverse effects

Preclinical, phase I, and phase II clinical trials indicated that tirzepatide exhibits adverse effects similar to those of other established GLP-1 receptor agonists, such as dulaglutide. These effects occur largely within the gastrointestinal tract.[25] The most frequently observed are nausea, diarrhea, and vomiting, which increased in incidence with the dosage amount (i.e. higher likelihood the higher the dose). The number of patients who discontinued taking tirzepatide also increased as dosage increased, with patients taking 15 mg having a 25% discontinuation rate vs 5.1% for 5 mg patients and 11.1% for dulaglutide.[26] To a slightly lesser extent, patients also reported reduced appetite. Other side effects reported were dyspepsia, constipation, abdominal pain, dizziness, and hypoglycaemia.[27] [28]

Pharmacology

Tirzepatide is an analogue of gastric inhibitory polypeptide (GIP), a human hormone that stimulates the release of insulin from the pancreas. Tirzepatide is a linear polypeptide of 39 amino acids that has been chemically modified by lipidation to improve its uptake into cells and its stability to metabolism.[29] It completed phase III trials globally in 2021.[30] [31]

Mechanism of action

Tirzepatide has a greater affinity to GIP receptors than to GLP-1 receptors, and this dual agonist behavior has been shown to produce greater reductions of hyperglycemia compared to a selective GLP-1 receptor agonist.[32] Signaling studies reported that tirzepatide mimics the actions of natural GIP at the GIP receptor.[33] At the GLP-1 receptor, though, tirzepatide shows bias towards cAMP (a messenger associated with regulation of glycogen, sugar, and lipid metabolism) generation, rather than β-arrestin recruitment. This combination of preference towards GIP receptor and distinct signaling properties at GLP-1 suggest this biased agonism increases insulin secretion. Tirzepatide has been reported to increase levels of adiponectin, an adipokine involved in the regulation of both glucose and lipid metabolism, with a maximum increase of 26% from baseline after 26 weeks, at the 10 mg dosage.

Chemistry

Structure

Tirzepatide is an analog of the human GIP hormone with a C20 fatty diacid portion attached, used to optimise the uptake and metabolism of the compound. The fatty-diacid section (eicosanedioic acid) is linked via a glutamic acid and two (2-(2-aminoethoxy)ethoxy)acetic acid units to the side chain of the lysine residue. This arrangement allows for a much longer half-life, extending the time between doses, because of its high affinity to albumin.[34]

Synthesis

The synthesis of tirzepatide was first disclosed in patents filed by Eli Lilly and Company.[35] This uses standard solid phase peptide synthesis, with an allyloxycarbonyl protecting group on the lysine at position 20 of the linear chain of amino acids, allowing a final set of chemical transformations in which the sidechain amine of that lysine is derivatized with the lipid-containing fragment.

Large-scale manufacturing processes have been reported for this compound.[36]

History

Eli Lilly and Company first applied for a patent for a method of glycemic control using tirzepatide in early 2016. The patent was published late that year. After passing phase III clinical trials, Eli Lilly applied for FDA approval in October 2021, with a priority review voucher.[37]

Following the completion of the SURPASS-2 trial (NCT03987919), the company announced in April 2022 that tirzepatide had successfully met their endpoints in obese and overweight patients without diabetes.[38]

In industry-funded preliminary trials comparing tirzepatide to the existing diabetes medication semaglutide (an injected analogue of the hormone GLP-1), tirzepatide showed minor improvement of reductions (2.01%–2.30% depending on dosage) in glycated hemoglobin tests relative to semaglutide (1.86%).[39] A 10 mg dose has also been shown to be effective in reducing insulin resistance, with a reduction of around 8% from baseline, measured using HOMA2-IR (computed with fasting insulin). Fasting levels of IGF binding proteins such as IGFBP1 and IGFBP2 increased following tirzepatide treatment, increasing insulin sensitivity.

The FDA approved tirzepatide based on evidence from nine clinical trials of 7,769 participants with type 2 diabetes, of which 5,415 of these participants received tirzepatide.[40] The trials were conducted at 673 sites in 24 countries, including Argentina, Australia, Brazil, Canada, India, Israel, Japan, Mexico, Russian Federation, South Korea, Taiwan, European Union, and the United States (including Puerto Rico). All nine trials were used to assess safety and five of these trials were used to assess the efficacy of tirzepatide. The five trials used in the efficacy evaluation included 6,263 adult participants with type 2 diabetes. Four additional trials (NCT #03131687, NCT #03311724 NCT #03861052, NCT #03861039) were included in the safety evaluation, for a total of 7,769 adult participants with type 2 diabetes; therefore, the number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety. The benefits of tirzepatide for the treatment of adult participants with type 2 diabetes were primarily evaluated in five clinical trials. In two of these trials (NCT #03954834 and NCT #04039503), participants were randomly assigned to receive either tirzepatide or placebo injection weekly. Neither the patient nor the healthcare provider knew which treatment was being given until after the trials were completed. Treatment was given for 40 weeks. In the other three trials (NCT #3987919, 03882970, and 03730662), participants were randomly assigned to receive either tirzepatide or another antidiabetic medication, and the patient and provider knew which medication was being given. Treatment was given for 40 weeks to 104 weeks. In each trial, HbA1c was measured from the start of the trial to the end of the trial and compared between the tirzepatide group and the other groups.

The efficacy of tirzepatide for chronic weight management (weight reduction and maintenance) in combination with a reduced-calorie diet and increased physical activity was established in two randomized, double-blind, placebo-controlled trials of adults with obesity or overweight with at least one weight-related condition. These studies measured weight reduction after 72 weeks in a total of 2,519 participants who received either 5 mg, 10 mg or 15 mg of tirzepatide once weekly and a total of 958 participants who received once-weekly placebo injections. In both trials, after 72 weeks of treatment, participants who received tirzepatide at all three dose levels experienced a statistically significant reduction in body weight compared to those who received placebo, and greater proportions of participants who received tirzepatide achieved at least 5% weight reduction compared to placebo.

In August 2024, the SURMOUNT-1 three-year study (176-week treatment period) revealed that Tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight.[41]

Meta-analysis

A 2021 meta-analysis showed that over one year of clinical use, tirzepatide was observed to be superior to dulaglutide, semaglutide, degludec, and insulin glargine with regards to glycemic efficacy and obesity reduction.[42]

In a phase III double-blind, randomized, controlled trial supported by Eli Lilly, nondiabetic adults with a body mass index of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, were randomized to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo. The mean percentage change in weight at week 72 was −15.0% (95% confidence interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 15-mg doses. Weight change in the placebo group was −3.1% (95% CI, −4.3 to −1.9).[43] [44] [45]

Society and culture

Legal status

The FDA granted the application for tirzepatide priority review designation. The FDA approved Mounjaro for use in the United States in 2022.

In July 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Mounjaro, intended for the treatment of type2 diabetes.[46] Tirzepatide was approved for medical use in the European Union in September 2022.[47]

Brand names

Tirzepatide is the international nonproprietary name (INN).[48]

Tirzepatide is sold under the brand names Mounjaro and Zepbound.

Further reading

  • Bhagavathula AS, Vidyasagar K, Tesfaye W . Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials . Pharmaceuticals . 14 . 10 . September 2021 . 991 . 34681215 . 8537322 . 10.3390/ph14100991 . free . doi .
  • Frías JP . Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes . Expert Rev Endocrinol Metab . 15 . 6 . 379–394 . November 2020 . 33030356 . 10.1080/17446651.2020.1830759 . 222213936 .
  • Ryan DH . Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? . J Obes Metab Syndr . 30 . 3 . 196–208 . September 2021 . 34518444 . 8526285 . 10.7570/jomes21033 .

]

Notes and References

  1. Web site: Australian prescription medicine decision summaries: Mounjaro . Therapeutic Goods Administration . 28 February 2023 . 5 February 2023 . https://web.archive.org/web/20230205203609/https://www.tga.gov.au/resources/auspmd/mounjaro . live .
  2. Web site: Mounjaro tirzepatide 15 mg/0.5 mL solution for injection pre-filled pen (379334). Therapeutic Goods Administration. 28 February 2023. 3 January 2023. https://web.archive.org/web/20230103060331/https://www.tga.gov.au/resources/artg/379334. live.
  3. Web site: Public Summary: Mounjaro tirzepatide 15 mg/0.5 mL solution for injection pre-filled pen . Therapeutic Goods Administration . 28 February 2023 . 18 November 2023 . https://web.archive.org/web/20231118204708/https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=379334&agid=%28PrintDetailsPublic%29&actionid=1 . live .
  4. Web site: Details for: Mounjaro . . 24 November 2022 . 3 March 2024 . 10 March 2024 . https://web.archive.org/web/20240310061954/https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102190 . live .
  5. Web site: Notice: Multiple Additions to the Prescription Drug List (PDL) [2023-03-08] ]. . 8 March 2023 . 21 March 2023 . 22 March 2023 . https://web.archive.org/web/20230322024545/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/mutliple-additions-2023-03-08.html . live .
  6. Web site: Summary Basis of Decision - Mounjaro . . 17 March 2023 . 24 April 2023 . 25 April 2023 . https://web.archive.org/web/20230425010125/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00629&lang=en . live .
  7. Web site: Mounjaro 5mg solution for injection in pre-filled pen . (emc) . 16 November 2023 . 17 November 2023 . 27 June 2023 . https://web.archive.org/web/20230627111224/https://www.medicines.org.uk/emc/product/14205/smpc . live .
  8. Web site: Mounjaro 2.5mg solution for injection in pre-filled pen . (emc) . 16 November 2023 . 17 November 2023 . 6 August 2023 . https://web.archive.org/web/20230806082721/https://www.medicines.org.uk/emc/product/14206/smpc . live .
  9. Web site: Mounjaro- tirzepatide injection, solution . DailyMed . 13 May 2022 . 27 May 2022 . 3 July 2022 . https://web.archive.org/web/20220703054225/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0 . live .
  10. Web site: Zepbound- tirzepatide injection, solution . DailyMed . 9 November 2023 . 20 November 2023 . 20 November 2023 . https://web.archive.org/web/20231120051112/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b . live .
  11. Web site: Mounjaro EPAR . European Medicines Agency (EMA) . 18 July 2022 . 2 January 2023 . 12 December 2022 . https://web.archive.org/web/20221212220255/https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes . U.S. Food and Drug Administration (FDA) . 13 May 2022 . 13 May 2022 . 13 May 2022 . https://web.archive.org/web/20220513192349/https://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targeted-treatment-type-2-diabetes . live .
  13. 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 . December 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 . . 18 . 3–14 . 10.1016/j.molmet.2018.09.009 . 6308032 . 30473097 . free . doi .
  14. Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G . Tirzepatide: A Systematic Update . Int J Mol Sci . 23 . 23 . November 2022 . 14631 . 36498958 . 9741068 . 10.3390/ijms232314631 . free . doi .
  15. Web site: 10 March 2021 . Drug and Health Product Submissions Under Review (SUR): New drug submissions completed . 5 January 2023 . Health Canada . 5 January 2023 . https://web.archive.org/web/20230105002029/https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review/new-drug-submissions-completed.html . live .
  16. Web site: Advancing Health Through Innovation: New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . 10 January 2023 . 22 January 2023 . 21 January 2023 . https://web.archive.org/web/20230121035714/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022 . live .
  17. New Drug Therapy Approvals 2022 . U.S. Food and Drug Administration (FDA) . January 2024 . PDF . 14 January 2024 . https://web.archive.org/web/20240114065648/https://www.fda.gov/media/164429/download . 14 January 2024 . live .
  18. News: Kolata . Gina . F.D.A. Approves New Obesity Drug Tirzepatide That Will Compete With Wegovy . The New York Times . 8 November 2023 . 9 November 2023 . 9 November 2023 . https://web.archive.org/web/20231109002649/https://www.nytimes.com/2023/11/08/health/fda-tirzepatide-obesity-zepbound-wegovy.html . live .
  19. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss . GOV.UK . 8 November 2023 . 17 November 2023 . 16 November 2023 . https://web.archive.org/web/20231116014709/https://www.gov.uk/government/news/mhra-authorises-diabetes-drug-mounjaro-tirzepatide-for-weight-management-and-weight-loss . live .
  20. Web site: Constantino . Annika Kim . 17 April 2024 . Most doses of Eli Lilly's Zepbound, Mounjaro in short supply through June, FDA says . 18 April 2024 . CNBC .
  21. FDA Approves New Medication for Chronic Weight Management . U.S. Food and Drug Administration (FDA) . 8 November 2023 . 9 November 2023 . 8 November 2023 . https://web.archive.org/web/20231108210853/https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management . live .
  22. Web site: Chen . Elaine . 2024-08-01 . Eli Lilly's obesity drug Zepbound shows benefits in heart failure patients . 2024-08-01 . STAT . en-US.
  23. Web site: 2024-08-01 . Eli Lilly's tirzepatide cuts heart failure risks, company says . 2024-08-01 . NBC News . en.
  24. News: Lilly's tirzepatide successful in phase 3 study showing benefit in adults with heart failure with preserved ejection fraction and obesity . Eli Lilly and Company . 1 August 2024.
  25. Min T, Bain SC . The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials . Diabetes Therapy . 12 . 1 . 143–157 . January 2021 . 33325008 . 7843845 . 10.1007/s13300-020-00981-0 . free . doi .
  26. Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, Gimeno RE, Milicevic Z, Robins D, Haupt A . 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 . . 392 . 10160 . 2180–2193 . November 2018 . 30293770 . 10.1016/S0140-6736(18)32260-8 . free . doi .
  27. Frias JP, Nauck MA, Van J, Benson C, Bray R, Cui X, Milicevic Z, Urva S, Haupt A, Robins DA . Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens . . 22 . 6 . 938–946 . June 2020 . 31984598 . 7318331 . 10.1111/dom.13979 . free . doi .
  28. Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á . 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 . . 327 . 6 . 534–545 . February 2022 . 35133415 . 10.1001/jama.2022.0078 . 8826179 .
  29. Ahangarpour M, Kavianinia I, Harris PW, Brimble MA . Photo-induced radical thiol-ene chemistry: a versatile toolbox for peptide-based drug design . . 50 . 2 . 898–944 . January 2021 . 33404559 . 10.1039/d0cs00354a . Royal Society of Chemistry . 230783854 .
  30. Tirzepatide significantly reduced A1C and body weight in people with type 2 diabetes in two phase 3 trials from Lilly's SURPASS program. Eli Lilly and Company. PR Newswire. 17 February 2021. 28 October 2021. 28 October 2021. https://web.archive.org/web/20211028002144/https://www.prnewswire.com/news-releases/tirzepatide-significantly-reduced-a1c-and-body-weight-in-people-with-type-2-diabetes-in-two-phase-3-trials-from-lillys-surpass-program-301229506.html. live.
  31. Web site: Lilly : Phase 3 Tirzepatide Results Show Superior A1C And Body Weight Reductions In Type 2 Diabetes. Business Insider. RTTNews. 19 October 2021. 28 October 2021. 28 October 2021. https://web.archive.org/web/20211028002143/https://markets.businessinsider.com/news/stocks/lilly-phase-3-tirzepatide-results-show-superior-a1c-and-body-weight-reductions-in-type-2-diabetes-1030876853. live.
  32. Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, Milicevic Z, Haupt A, Robins DA . Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes . . 106 . 2 . 388–396 . January 2021 . 33236115 . 7823251 . 10.1210/clinem/dgaa863 . free . doi .
  33. Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ, Holst JJ, D'Alessio DA, Coghlan MP, Rosenkilde MM, Campbell JE, Sloop KW . Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist . . 5 . 17 . September 2020 . 32730231 . 7526454 . 10.1172/jci.insight.140532 . free . doi .
  34. Østergaard S, Paulsson JF, Kofoed J, Zosel F, Olsen J, Jeppesen CB, Spetzler J, Ynddal L, Schleiss LG, Christoffersen BØ, Raun K, Sensfuss U, Nielsen FS, Jørgensen R, Wulff BS . October 2021 . The effect of fatty diacid acylation of human PYY3-36 on Y2 receptor potency and half-life in minipigs . . 11 . 1 . 21179 . 2021NatSR..1121179O . 10.1038/s41598-021-00654-3 . 8551270 . 34707178 . free . doi .
  35. US . 9474780 . patent . 2016-10-25 . 2016-01-05 . 2015-01-09 . Bokvist BK, Coskun T, Cummins RC, Alsina-Fernandez J . GIP and GLP-1 co-agonist compounds . Eli Lilly and Co .
  36. 10.1021/acs.oprd.1c00108 . Kilogram-Scale GMP Manufacture of Tirzepatide Using a Hybrid SPPS/LPPS Approach with Continuous Manufacturing . 2021 . Frederick MO, Boyse RA, Braden TM, Calvin JR, Campbell BM, Changi SM, Coffin SR, Condon C, Gowran O, McClary Groh J, Groskreutz SR, Harms ZD, Humenik AA, Kallman NJ, Klitzing ND, Kopach ME, Kretsinger JK, Lambertus GR, Lampert JT, Maguire LM, Moynihan HA, Mullane NS, Murphy JD, O'Mahony ME, Richey RN, Seibert KD, Spencer RD, Strege MA, Tandogan N, Torres FL . Organic Process Research & Development. 25 . 7 . 1628–1636 . 237690232 .
  37. News: Sagonowsky . Eric . 26 October 2021 . As Lilly gears up for key 2022 launches, Trulicity, Taltz and more drive solid growth . 9 April 2022 . Fierce Pharma . 14 May 2022 . https://web.archive.org/web/20220514041302/https://www.fiercepharma.com/pharma/as-lilly-gears-up-for-key-2022-launches-its-existing-meds-post-solid-growth . live .
  38. Web site: Kellaher . Colin . 28 April 2022 . Eli Lilly's Tirzepatide Meets Main Endpoints in Phase 3 Obesity Study . 29 April 2022 . . . 29 April 2022 . https://web.archive.org/web/20220429031537/https://www.marketwatch.com/story/eli-lilly-s-tirzepatide-meets-main-endpoints-in-phase-3-obesity-study-lly-271651143389 . live .
  39. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K . Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes . . 385 . 6 . 503–515 . August 2021 . 34170647 . 10.1056/NEJMoa2107519 . 235635529 . free . doi .
  40. Web site: Drug Trials Snapshots: Mounjaro . U.S. Food and Drug Administration (FDA) . 13 June 2023 . 14 June 2023 . 9 November 2023 . https://web.archive.org/web/20231109045730/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-mounjaro . live .
  41. Web site: Tirzepatide reduced the risk of developing type 2 diabetes by 94% in adults with pre-diabetes and obesity or overweight .
  42. Dutta D, Surana V, Singla R, Aggarwal S, Sharma M . Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis. . . 25 . 6 . 475–489 . Nov–Dec 2021 . 10.4103/ijem.ijem_423_21 . 35355921 . 8959203 . free . doi .
  43. Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang SY, Liu B, Bunck MC, Stefanski A. 4 June 2022. 10.1056/NEJMoa2206038. NEJM. 387. 3. 205–216. 35658024. 249385412. free . doi .
  44. Web site: Dee. Jane E.. More Than 20% Weight Reduction in Individuals With Obesity. Yale Department of Internal Medicine. 6 June 2022. 12 June 2022. 10 June 2022. https://web.archive.org/web/20220610162308/https://medicine.yale.edu/intmed/news-article/new-medication-results-in-more-than-20-weight-reduction-in-individuals-with-obesity/. live.
  45. Web site: Davis. Nicola. Diabetes drug leads to notable weight loss in people with obesity – study. The Guardian. 5 June 2022. 12 June 2022. 11 June 2022. https://web.archive.org/web/20220611224045/https://www.theguardian.com/science/2022/jun/05/diabetes-drug-tirzepatide-leads-to-notable-weight-loss-in-people-with-obesity-study. live.
  46. Web site: 22 July 2022 . Mounjaro: Pending EC decision . live . https://web.archive.org/web/20220728165617/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/mounjaro . 28 July 2022 . 30 July 2022 . European Medicines Agency. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  47. Web site: Mounjaro Product information . Union Register of medicinal products . 3 March 2023 . 8 February 2023 . https://web.archive.org/web/20230208215548/https://ec.europa.eu/health/documents/community-register/html/h1685.htm . live .
  48. World Health Organization . ((World Health Organization)) . 2019 . International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81 . WHO Drug Information . 33 . 1 . free . 10665/330896.

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