Retatrud 50 mg

▎ Retatrutid Structure

Source: PubChem

Sequence: YA⊃1;QGTFTSDYSI-L⊃2;LDKK⁴AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Molecular Formula: C 221H 342N 46O68 Molecular Luj: 4731 g / mol CAS Nr .: 2381089-83-2 PubChem CID: 171390338 Synonyms: LY3437943

▎ Retatrutid Research

Kev tshawb fawb keeb kwm ntawm Retatrutid yog dab tsi?

Kev rog rog tau dhau los ua ib qho ntawm cov teeb meem kev noj qab haus huv tseem ceeb hauv zej zog niaj hnub no. Nws tuaj yeem ua rau muaj teeb meem kev noj qab haus huv ntau yam xws li hom 2 mob ntshav qab zib mellitus, kab mob plawv, ntshav siab, dyslipidemia, thiab kab mob tsis muaj dej cawv fatty siab. Nrog rau qhov nce ntxiv ntawm qhov tshwm sim ntawm kev rog rog, muaj qhov xav tau ceev ceev rau cov kev kho tshiab uas tuaj yeem tswj hwm lub cev hnyav thiab txhim kho kev noj qab haus huv ^[1] . Txawm hais tias kev cuam tshuam hauv kev ua neej, xws li kev ua kom lub cev muaj zog thiab tswj kev noj zaub mov, yog qhov tseem ceeb rau kev ntsuas qhov hnyav, nws nyuaj heev rau ntau tus neeg mob rog rog kom tswj tau qhov hnyav mus ntev.

Retatrutid, raws li tus tshiab triple receptor agonist, tuaj yeem ua rau ntawm glucagon-zoo li peptide-1 receptor (

GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), thiab glucagon receptor (GCGR). Qhov no multi-receptor mechanism ntawm kev nqis tes ua endows nws nrog cov txiaj ntsig tseem ceeb hauv kev poob phaus. Piv nrog rau cov tshuaj poob phaus uas ua rau tsuas yog ib qho receptor, Retatrutid tuaj yeem tswj hwm lub cev cov txheej txheem metabolic ^[1] . Retatrutid ua tiav qhov poob phaus los ntawm kev tswj hwm ntau cov tshuaj hormones receptors, tsis yog tsuas yog qhia tau hais tias muaj txiaj ntsig zoo, tab sis kuj muaj kev mob plab me me. Tsis tas li ntawd, raws li ib tug triple receptor agonist, Retatrutid muaj ib tug muaj zog poob yuag nyhuv thiab ib tug ntau yam ntawm cov neeg siv piv nrog rau lwm yam tshiab yuag tshuaj.

Retatrutid yog dab tsi?

Retatrutid yog ib qho tshiab ntev-ua yeeb yam glucagon-zoo li peptide-1 (GLP-1) receptor agonist. Nws tau hloov kho thiab ua kom zoo raws li cov qauv ntawm ntuj GLP-1, thiab nws tuaj yeem khi rau thiab ua kom lub GLP-1 receptor, ua haujlwm lub cev zoo ib yam li cov natural GLP-1, xws li kev txhawb nqa insulin secretion, inhibiting glucagon secretion, qeeb gastric emptying, txo qab los noj mov, thiab lwm yam.

Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm Retatrutid?

Lub mechanism ntawm kev txiav txim ntawm Retatrutid stems los ntawm nws agonistic teebmeem ntawm ntau receptors. Ua ntej, nws cov nyhuv agonistic ntawm glucagon-zoo li peptide-1 receptor (GLP-1R) tuaj yeem ua rau cov tshuaj insulin ntau ntxiv, inhibit glucagon secretion, txo cov ntshav qabzib, thiab tib lub sijhawm ncua kev ua pa ntawm plab, ua kom satiety, thiab txo cov zaub mov noj ^[2] . Qhov thib ob, nws cov nyhuv agonistic ntawm cov piam thaj-dependent insulinotropic polypeptide receptor (GIPR) tuaj yeem txhawb kev tsim cov tshuaj insulin, txhim kho kev siv cov piam thaj, thiab cuam tshuam rau cov metabolism hauv rog, inhibiting lipolysis thiab txhawb kev rog rog ^[2] . Ntxiv mus, cov nyhuv agonistic ntawm Retatrutid ntawm glucagon receptor (GCGR) feem ntau txhawb nqa glycogenolysis thiab gluconeogenesis hauv daim siab, ua rau cov ntshav qabzib nce ntxiv. Txawm li cas los xij, nyob rau hauv qhov kev txiav txim ntawm Retatrutid, qhov no cov piam thaj-tso cov nyhuv yog offset los ntawm cov teebmeem ntawm lwm tus ob receptors, thaum txhawb lipolysis thiab txo cov rog rog ^[2] . Qhov ntau hom phiaj ntawm qhov kev ua no yuav ua tau zoo dua hauv kev kho mob rog dua li ib leeg receptor agonists.

Los ntawm tib lub sijhawm ua rau peb cov receptors no, Retatrutid tuaj yeem siv ntau yam kev tswj hwm cov metabolism thiab tsim cov teebmeem kev noj qab haus huv ntawm kev rog rog thiab cov kab mob ntsig txog. Raws li kev tswj hwm cov ntshav qabzib, txij li kev ua kom GLP-1R thiab GIPR txhawb nqa insulin secretion thiab inhibits glucagon secretion, thiab kev ua haujlwm ntawm GCGR raug cuam tshuam los ntawm cov teebmeem ntawm ob lub receptors, Retatrutid tuaj yeem tswj cov ntshav qabzib ntau, uas yog qhov tseem ceeb rau kev kho mob ntawm hom 2 mob ntshav qab zib ^mellitus . Nyob rau hauv cov nqe lus ntawm kev txo cov rog tsub zuj zuj, qhov ua rau ntawm GCGR txhawb lipolysis thiab txo cov rog tsub kom, thaum lub activation ntawm GLP-1R tsub kom satiety thiab txo cov zaub mov noj, ntxiv txo cov rog synthesis ^[1] . Tsis tas li ntawd, Retatrutid kuj tseem muaj kev txhim kho ntawm cov kab mob uas tsis yog-alcoholic fatty siab. Nws tuaj yeem txo cov rog hauv daim siab thiab txhim kho daim siab ua haujlwm.

HbA1c, lub cev hnyav, ntshav siab, thiab lipids Cov ntaub ntawv yog qhov tsawg tshaj plaws-squares txhais tau tias (nrog cov kab yuam kev uas qhia SEs) los ntawm kev tsom xam ua tau zoo, tshwj tsis yog sau tseg.

Source: PubMed ^[4]

Hauv dab tsi ua Retatrutid qhia nws cov teebmeem?

Retatrutid nthuav tawm cov teebmeem tseem ceeb hauv ntau yam

Kev poob ceeb thawj tseem ceeb: Retatrutid tau ua kom pom qhov hnyav hnyav hauv ntau qhov kev sim tshuaj. Piv txwv li, hauv kev tshawb fawb soj ntsuam nrog rau 338 tus neeg laus (Jastreboff AMM, 2023), cov neeg mob kho nrog ntau koob tshuaj Retatrutid tau poob ceeb thawj ntawm 48 lub lis piam. Ntawm lawv, cov neeg mob hauv pawg koob tshuaj 12mg poob 24.2% ntawm lawv lub cev hnyav, thiab feem ntau ntawm cov neeg mob tau poob phaus mus rau qhov sib txawv. Piv txwv li, ntawm cov neeg mob tau txais koob tshuaj 4mg, 8mg, thiab 12mg, 92%, 100%, thiab 100% ntawm cov neeg mob, raws li, poob 5% lossis ntau dua ntawm lawv lub cev hnyav. Hauv lwm txoj kev tshawb fawb ^[3] , ob qhov kev sim tshuaj ntsuam xyuas uas suav nrog 353 tus neeg mob uas muaj hom 2 mob ntshav qab zib mellitus tau pom tias piv nrog cov placebo, Retatrutid tuaj yeem txo lub cev hnyav ntawm cov neeg mob los ntawm 11.89kg, thiab tseem txo glycated hemoglobin (HbA1C). Tsis tas li ntawd, hauv kev sim cov neeg laus uas muaj kev rog rog yam tsis muaj ntshav qab zib, Retatrutid ua rau 24.2% poob rau cov neeg mob, thiab 83% ntawm cov neeg mob poob 15% lossis ntau dua ntawm lawv lub cev hnyav ntawm 48 lub lis piam. Cov txiaj ntsig no qhia tau tias Retatrutid muaj peev xwm loj hauv kev poob phaus.

Kev kho mob ntawm hom 2 mob ntshav qab zib mellitus: Retatrutid kuj qhia tau qee yam muaj peev xwm hauv kev kho mob ntshav qab zib hom 2. Hauv qee qhov kev sim tshuaj, Retatrutid tau qhia txog kev txo qis hauv glycated hemoglobin (HbA1c) thiab kev poob phaus ntawm koob tshuaj. Piv txwv li, nyob rau hauv ib txoj kev tshawb no, nyob rau hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus, Retatrutid pom tau hais tias muaj kev cuam tshuam cov ntshav qabzib. Piv nrog rau cov placebo, glycated hemoglobin poob los ntawm 1.64% ^[3] . Tsis tas li ntawd, nyob rau hauv randomized, ob-dig muag, placebo thiab active-tswj parallel-paj pawg theem 2 mus sib hais, tsiaj cov qauv nrog hom 2 mob ntshav qab zib mellitus, tom qab tau txais kev kho mob Retatrutid, pom qhov txo qis hauv glycated hemoglobin qib, thiab lawv lub cev hnyav kuj tau txo qis hauv kev siv tshuaj ntau npaum li cas ^[4] . Qhov no tuaj yeem raug ntaus nqi los ntawm cov txiaj ntsig zoo ntawm cov tshuaj ntawm GLP-1, GCGR, thiab GIPR, uas txhim kho cov piam thaj metabolism thiab lub zog sib npaug.

Kev txhim kho ntawm cov kab mob plawv: Retatrutid tuaj yeem tsis tsuas yog txo lub cev hnyav xwb tab sis kuj txhim kho cov kab mob plawv, xws li cov ntshav lipid profile thiab qib glycated hemoglobin. Qhov no qhia txog kev sib txuas ntawm pathophysiological ze ntawm kev rog thiab cov kab mob plawv, thiab Retatrutid tuaj yeem txhim kho cov hlab plawv kev noj qab haus huv ntawm cov neeg mob rog dhau los ntawm ntau txoj hauv kev. Piv txwv li, txo qis HDL-C, apoB, thiab LDLP qib tuaj yeem txo qhov kev pheej hmoo ntawm atherosclerosis; txo glycated hemoglobin qib tuaj yeem txhim kho kev tswj ntshav qabzib hauv cov neeg mob ntshav qab zib, yog li txo qis kev pheej hmoo ntawm cov teeb meem plawv ^{[3, 5, 6]}.

Kev kho mob ntawm cov kab mob uas tsis yog-alcoholic fatty siab (NAFLD): Retatrutid yog ib qho tshiab triple receptor agonist peptide uas tsom rau glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), thiab glucagon-zoo li peptide-1 receptor (GLP-1R). Cov kev tshawb fawb tau pom tias Retatrutid muaj peev xwm kho tau cov kab mob uas tsis yog-alcoholic fatty siab. Hauv ib txoj kev tshawb fawb, ib qho kev sib tw, ob qhov muag tsis pom kev, kev sim tshuaj placebo tau ua rau 48 lub lis piam rau cov neeg koom nrog cov kab mob metabolic-uas cuam tshuam nrog fatty siab mob thiab lub siab rog cov ntsiab lus ntawm ≥10%. Cov txiaj ntsig tau pom tias ntawm 24 lub lis piam, qhov nruab nrab ntawm cov txheeb ze hloov pauv hauv daim siab rog los ntawm cov hauv paus hauv paus hauv cov neeg koom nrog cov tshuaj sib txawv ntawm Retatrutid (1mg, 4mg, 8mg, thiab 12mg) yog -42.9%, -57.0%, -81.4%, thiab -82.4%, feem, thaum nyob hauv pawg placebo yog +0.3 ^% . Qhov no qhia tau hais tias Retatrutid tuaj yeem muaj kev kho mob tseem ceeb ntawm cov kab mob uas tsis yog-alcoholic fatty siab.

Hauv kev xaus, raws li tus tshiab triple receptor agonist, Retatrutid qhia tau hais tias muaj peev xwm loj hauv kev kho mob rog thiab lwm yam kab mob. Nws tuaj yeem tswj hwm tib neeg cov metabolism los ntawm ntau qhov ntev los ntawm kev ua kom cov glucagon receptor, qabzib-nyob ntawm insulinotropic polypeptide receptor, thiab glucagon-zoo li peptide-1 receptor, txhim kho ntshav qabzib tswj, txo lub cev hnyav, thiab tswj lipid metabolism. Qhov tshwm sim ntawm Retatrutid tau coj cov kev kho mob tshiab rau cov neeg mob rog rog, hom 2 mob ntshav qab zib mellitus, thiab lwm yam. Nws xav tias yuav tawg los ntawm cov kev txwv ntawm cov tshuaj ib txwm siv tshuaj receptor agonist, muab riam phom muaj zog dua rau kev daws cov teeb meem hnyav ntxiv ntawm kev rog rog thiab cov kab mob metabolic, txhawb kev txhim kho ntxiv ntawm kev kho mob, txhim kho lub neej zoo ntawm cov neeg mob.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Rosenstock J yog tus kws tshawb fawb muaj txiaj ntsig zoo hauv kev kho mob, sib koom tes nrog cov koom haum xws li University of Texas Southwestern Medical Center thiab University of Texas Dallas. Nws kuj ua kev tshawb fawb ntawm cov chaw xws li Canadian VIGOR Center thiab Veloc Clin Res Ctr Med City. 

Nws txoj kev tshawb fawb nthuav dav endocrinology thiab cov metabolism, kab mob plawv thiab mob plawv, kws tshuaj, thiab kev sim tshuaj, nrog rau kev tsom mus rau ntshav qab zib, rog rog, thiab lwm yam kev kho mob thiab kev txhim kho tshuaj. J Rosenstock tau ua tiav cov txiaj ntsig tseem ceeb hauv cov tshuaj kho mob, tau raug hu ua Tus Kws Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Plaws los ntawm 2017 txog 2024. Qhov no qhia txog qhov cuam tshuam loj thiab kev lees paub dav ntawm nws txoj haujlwm. Los ntawm kev koom tes nrog ntau lub koom haum tshawb fawb, nws tau ua tiav cov txiaj ntsig kev tshawb fawb hauv kev tshawb fawb hauv kev siv tshuaj kho mob, tau txais txiaj ntsig zoo rau cov neeg mob metabolic thiab kab mob plawv thiab nce qib kev kho mob. Rosenstock J tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [4].

▎ Cov Lus Qhia Tseem Ceeb

[1] Kaur M. European Journal of Clinical Pharmacology, 2024,80(5):669-676.DOI:10.1007/s00228-024-03646-0.

[2] Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-Receptor Agonist Retatrutid for Obesity - Phase 2 Trial [J]. New England Journal of Medicine, 2023,389(6:514-526.DOI:10.1056/NEJMoa2301972.

[3] Lopez DC, Pajimna JT, Milan MD, et al. 7792 Kev Ua Tau Zoo ntawm Retatrutid rau Kev Txo Nyhav thiab Nws Cov Teebmeem Cardiometabolic Ntawm Cov Neeg Laus: Kev Ntsuam Xyuas Txheej Txheem thiab Meta-Analysis[J]. Phau ntawv Journal of the Endocrine Society, 2024,8(1):163-749.DOI:10.1210/jendso/bvae163.749.

[4] Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutid, GIP, GLP-1 thiab glucagon receptor agonist, rau cov neeg mob ntshav qab zib hom 2: ib qho randomised, ob-dig muag, placebo thiab active-tswj, parallel-pab pawg, theem 2 sim ua nyob rau hauv teb chaws USA [J]. Lancet, 2023,402(10401):529-544.DOI:10.1016/S0140-6736(23)01053-X.

[5] Nicholls S, Pirro V, Lin Y, et al. Triple-hormone receptor agonist retatrutide ua haujlwm tau zoo txhim kho lipoprotein thiab apolipoprotein profiles hauv cov neeg koom nrog rog lossis rog [J]. European Heart Journal, 2024,45.DOI:10.1093/eurheartj/ehae666.1501.

[6] Ray A. Retatrutid: triple incretin receptor agonist rau kev tswj kev rog [J]. Cov Lus Qhia Txog Kev Tshawb Fawb Txog Tshuaj, 2023,32(11): 1003-1008.DOI: 10.1080/13543784.2023.2276754.

[7] Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide rau metabolic dysfunction-associated steatotic siab kab mob: randomized theem 2a sim [J]. Nature Medicine, 2024,30(7):2037-2048.DOI:10.1038/s41591-024-03018-2.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.