Retatrud 10 mg

▎ Retatrutid Structure

▎ Retatrutid Research

Kev tshawb fawb keeb kwm ntawm Retatrutid yog dab tsi?

Kev rog rog yog ib qho teeb meem kev noj qab haus huv loj rau pej xeem niaj hnub no. Kev rog rog tuaj yeem ua rau muaj ntau yam teeb meem kev noj qab haus huv, xws li hom 2 metabolism, kab mob plawv, ntshav siab, dyslipidemia, thiab kab mob siab tsis muaj dej cawv. Nrog rau kev nce ntxiv ntawm qhov tshwm sim ntawm kev rog, muaj kev xav tau ntau ntxiv 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 hloov kho txoj kev ua neej, xws li kev ua kom lub cev muaj zog thiab txo cov zaub mov noj, yog thawj txoj hauv kev rau kev tswj qhov hnyav, kev saib xyuas lub sij hawm ntev ntawm kev poob phaus tseem yog qhov nyuaj rau ntau tus neeg laus. Retatrutid yog ib qho tshiab triple receptor agonist uas ua haujlwm 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 txiav txim muab nws tshwj xeeb zoo hauv kev poob phaus. Piv nrog rau cov tshuaj poob phaus uas ua rau ib leeg 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 yam tshuaj hormones. Nws tsis tsuas yog muaj txiaj ntsig zoo rau kev poob phaus tab sis kuj muaj cov kev mob tshwm sim me me hauv plab hnyuv. Tsis tas li ntawd, piv nrog rau lwm cov tshuaj poob phaus tshiab, Retatrutid, raws li triple receptor agonist, muaj qhov hnyav dua qhov hnyav dua thiab ntau dua ntawm cov neeg siv.

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

Cov txheej txheem ntawm kev txiav txim ntawm Retatrutid feem ntau tshwm sim los ntawm nws cov teebmeem agonistic ntawm ntau tus receptors. Ua ntej, nws cov nyhuv agonistic ntawm glucagon-zoo li peptide-1 receptor (GLP-1R) nce insulin secretion, inhibits glucagon secretion, txo cov ntshav qabzib, thiab tib lub sijhawm qeeb plab hnyuv, nce 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 nqa cov tshuaj insulin, txhim kho kev siv cov piam thaj, thiab muaj kev cuam tshuam rau cov roj metabolism, inhibiting lipolysis thiab txhawb kev rog rog ^[2] . Ntxiv mus, txawm hais tias cov nyhuv agonistic ntawm Retatrutid ntawm glucagon receptor (GCGR) feem ntau txhawb nqa glycogenolysis thiab gluconeogenesis hauv daim siab, nce ntshav qabzib ntau ntau, raws li qhov kev txiav txim ntawm Retatrutid, cov nyhuv ntawm kev nce ntshav qabzib yog offset los ntawm cov teebmeem ntawm ob lub receptors. Nyob rau tib lub sijhawm, nws 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. Nyob rau hauv cov nqe lus ntawm kev tswj cov ntshav qabzib, vim qhov ua rau ntawm GLP-1R thiab GIPR txhawb insulin secretion thiab inhibiting glucagon secretion, thiab kev ua kom GCGR raug offset los ntawm cov teebmeem ntawm ob receptors, Retatrutid tuaj yeem tswj cov ntshav qabzib ntau, uas yog qhov tseem ceeb rau kev kho mob ntawm hom ² . 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 zuj zuj. Nyob rau tib lub sijhawm, qhov ua rau GLP-1R nce satiety thiab txo cov khoom noj, ntxiv txo cov rog synthesis ^{[1, 2]} . Tsis tas li ntawd, Retatrutid kuj muaj txiaj ntsig zoo rau cov kab mob tsis muaj dej cawv fatty siab. Nws tuaj yeem txo cov rog hauv daim siab thiab txhim kho daim siab ua haujlwm. Ib qho randomized, ob-dig muag, kev sim tshuaj placebo tau pom tias qhov nruab nrab ntawm cov txheeb ze hloov pauv hauv daim siab rog hauv pab pawg kho Retatrutid ntawm 24 lub lis piam tau qis dua li hauv pawg placebo ^[3].

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]

Yuav ua li cas raws nraim Retatrutid tswj cov piam thaj metabolism tom qab ua kom peb receptors?

Retatrutid tswj cov ntshav qabzib los ntawm ntau lub tswv yim, suav nrog kev ua kom GLP-1 thiab GIP receptors, txhawb kev tsim cov tshuaj insulin, inhibiting glucagon secretion, qeeb plab hnyuv, tswj cov roj metabolism, thiab txo qis ANGPTL3/8 qib. Raws li kev tswj hwm cov ntshav qabzib, Retatrutid ua rau GLP-1 thiab GIP receptors, txhawb kev nkag siab ntawm pancreatic β hlwb rau cov piam thaj, ua kom cov piam thaj thiab tso tawm cov tshuaj insulin, thiab tom qab ntawd txhawb kev nce thiab siv cov piam thaj los ntawm cov ntaub so ntswg, ua tiav cov txiaj ntsig ntawm kev txo cov ntshav qabzib ^{[4, 5, 2.} Cov txiaj ntsig tseem ceeb ntawm kev txo qis glycated hemoglobin (HbA1c), uas feem ntau tau txais txiaj ntsig los ntawm nws lub luag haujlwm hauv stimulating insulin secretion (Rosenstock J, 2023). Nyob rau tib lub sijhawm, ua kom cov GLP-1 receptor tuaj yeem cuam tshuam qhov tso tawm ntawm glucagon los ntawm pancreatic α hlwb, tiv thaiv cov ntshav qabzib kom siab dhau. Hauv kev tshawb fawb soj ntsuam, nws tau pom tias cov qib glucagon ntawm cov neeg mob siv Retatrutid tau txo qis, uas ua rau kom muaj kev ruaj ntseg ntawm cov ntshav qabzib ^{[4, 5]} . Ua kom muaj GLP-1 thiab GIP receptors tuaj yeem ncua qhov kev ua pa ntawm plab, ua rau qeeb qeeb thiab nqus cov zaub mov, thiab txo qis qis hauv cov ntshav qabzib tom qab. Cov kev tshawb fawb tau pom tias lub sijhawm ua pa ntawm lub plab ntawm cov neeg mob kho nrog Retatrutid tau ntev heev tom qab noj mov, yog li txo qis tus nqi siab tshaj ntawm cov ntshav qabzib tom qab ^[4].

Cov kev cai ntawm cov roj metabolism los ntawm Retatrutid tseem cuam tshuam rau cov piam thaj metabolism. Piv txwv li, hauv kev tshawb fawb ntawm cov neeg mob rog rog, nws tau pom tias Retatrutid tuaj yeem txo qis triglycerides (TG), low-density lipoprotein (LDL), thiab cov lipoprotein tsawg-density (VLDL) cholesterol ^{[2, 6]} . Qhov kev txhim kho hauv lipid metabolism tuaj yeem cuam tshuam nrog kev txhim kho ntawm insulin rhiab heev, yog li pab tswj cov ntshav qabzib. Tshwj xeeb, tom qab kev kho Retatrutid, plasma 3-hydroxybutyric acid (3-HB) nce, nrog rau kev nce hauv 3-hydroxybutyrylcarnitine (C ₄OH), qhov piv ntawm acetylcarnitine rau dawb carnitine (C ₂/ C ₀), thiab nruab nrab-chain acyladicarnitine lipolysis ntawm cov ntaub so ntswg muaj zog. oxidation.

Retatrutid tseem tuaj yeem txo tag nrho cov dihydroceramides (DhCers), thiab qhov kev hloov pauv no cuam tshuam nrog kev txhim kho insulin rhiab heev, txo qis hepatic steatosis, thiab kab mob hauv lub cev ^[6] .Tam sim no, Retatrutid tuaj yeem txo qhov concentration ntawm ANGPTL3/8 complex hauv cov ntshav ntawm hom 2 metabolism hauv cov neeg mob, regulating ^. qabzib ANGPTL3/8 yog qhov zoo tshaj plaws circulating inhibitor ntawm lipoprotein lipase (LPL), thiab nws cov qib ntshav muaj feem cuam tshuam ncaj qha rau TG thiab qis lipoprotein cholesterol (LDL-C). Retatrutid txo qis ANGPTL3/8, uas tuaj yeem tswj cov piam thaj metabolism los ntawm kev txo qis triglyceride-nplua nuj lipoproteins ^[7] .

Hauv dab tsi ua Retatrutid qhia nws cov teebmeem?

Qhov tseem ceeb yuag poob nyhuv: 

Retatrutid tau pom qhov poob ceeb thawj tseem ceeb hauv ntau qhov kev sim tshuaj. Piv txwv li, hauv kev tshawb fawb soj ntsuam nrog 338 tus neeg laus ^[2] , cov neeg mob kho nrog cov tshuaj sib txawv ntawm Retatrutid tau poob ceeb thawj ntawm 48 lub lis piam. Ntawm lawv, cov neeg mob hauv pawg koob tshuaj 12mg tau poob qis ntawm 24.2%, thiab feem ntau ntawm cov neeg mob tau poob phaus mus rau qhov sib txawv. Piv txwv li, ntawm cov neeg mob tau txais 4mg, 8mg, thiab 12mg koob, 92%, 100%, thiab 100% ntawm cov neeg mob poob 5% lossis ntau dua ntawm lawv lub cev hnyav, raws li. Hauv lwm txoj kev tshawb fawb ^[8] , ob qhov kev sim tswj kev sib tw nrog 353 hom 2 cov neeg mob metabolism tau pom tias piv nrog cov placebo, Retatrutid tuaj yeem txo lub cev hnyav ntawm cov neeg mob los ntawm 11.89kg thiab txo glycated hemoglobin (HbA1C). Tsis tas li ntawd, hauv kev sim ntawm cov neeg laus uas tsis muaj ntshav qab zib rog rog, Retatrutid ua rau poob phaus ntawm 24.2% hauv 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 metabolism : 

Retatrutid kuj qhia tau qee yam muaj peev xwm hauv kev kho mob ntawm hom 2 metabolism. 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 hom 2 cov neeg mob metabolism, Retatrutid tau pom muaj kev tswj cov ntshav qabzib tseem ceeb, txo glycated hemoglobin los ntawm 1.64% piv nrog cov placebo ^{[4, 8]} . Tsis tas li ntawd, nyob rau hauv randomized, ob-dig muag, placebo, thiab active-tswj parallel-pab pawg theem 2 mus sib hais, tsiaj cov qauv nrog hom 2 metabolism tau pom qhov txo qis hauv glycated hemoglobin qib thiab qhov hnyav npaum li cas tom qab tau txais kev kho Retatrutid ^[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 teeb meem plawv plawv: 

Retatrutid tuaj yeem tsis tsuas yog txo lub cev hnyav xwb tab sis kuj tseem txhim kho cov kab mob plawv, xws li ntshav lipid profile thiab glycated hemoglobin qib. Qhov no qhia tau hais tias muaj kev sib raug zoo ntawm kev sib raug zoo ntawm kev rog 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 cov ntshav qabzib tswj hauv cov neeg mob metabolism, yog li txo qis kev pheej hmoo ntawm cov teeb meem plawv ^[8-10] .

Kev kho mob uas tsis yog-alcoholic fatty siab kab mob (NAFLD): 

Retatrutid yog ib qho tshiab triple receptor agonist peptide uas tsom rau glucagon receptor (GCGR), qabzib-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 kav ntev li 48 lub lis piam tau ua rau cov neeg koom nrog cov kab mob metabolic cuam tshuam nrog cov kab mob fatty siab thiab lub siab rog cov ntsiab lus ntawm ≥10%. Cov txiaj ntsig tau pom tias ntawm 24 lub lis piam, qhov nruab nrab hloov pauv hauv daim siab rog piv rau cov hauv paus hauv cov neeg koom nrog kev sib txawv ntawm cov tshuaj 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 qhib lub glucagon receptor, qabzib-nyob ntawm insulinotropic polypeptide receptor, thiab glucagon-zoo li peptide-1 receptor, kev tswj hwm lub cev metabolism los ntawm ntau qhov ntev, txhim kho ntshav qabzib tswj, txo lub cev hnyav, thiab tswj cov lipid metabolism. Qhov tshwm sim ntawm Retatrutid coj cov kev kho mob tshiab rau cov neeg mob rog rog, hom 2 metabolism, thiab lwm yam kab mob. Nws yuav tsum tau ua txhaum los ntawm cov kev txwv ntawm ib txwm siv tshuaj receptor agonist, muab riam phom muaj zog dua rau kev daws cov teeb meem loj zuj zus ntawm kev rog thiab cov kab mob metabolic, txhawb kev txhim kho ntxiv ntawm kev kho mob, txhim kho lub neej zoo ntawm cov neeg mob, thiab txo cov kev mob nkeeg hauv zej zog.

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, cov hlab plawv thiab cov hlab plawv, pharmacology, thiab kev sim tshuaj, nrog rau kev tsom mus rau cov metabolism, 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-A Phase 2 Trial [J]. New England Journal of Medicine, 2023,389(6:514-526.DOI:10.1056/NEJMoa2301972.

[3] 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.

[4] Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutid, GIP, GLP-1 thiab glucagon receptor agonist, rau cov neeg uas muaj hom 2 metabolism: 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] Brzozowska P, Frańczuk A, Nowińska B, et al. Retatrutid - revolutionary nyuam qhuav tsim GLP agonist - cov ntaub ntawv tshuaj xyuas [J]. Zoo hauv Kev Ua Si, 2024.DOI: 10.12775/qs.2024.15.52125.

[6] Pirro V, Pearson MJ, Lin Y, et al. Cov teebmeem ntawm Triple-hormone Receptor Agonist Retatrutid ntawm Lipid Profiling hauv Cov Neeg Koom Nrog Kev rog [J]. Metabolism, 2024,73.DOI:10.2337/db24-117-OR.

[7] Wen Y, Lemen D, Chen Y, et al. Kev txo qis ntawm triglyceride-nplua nuj lipoproteins nrog retatrutide hauv hom 2 metabolism tuaj yeem piav qhia los ntawm kev txo qis hauv ANGPTL3/8 qib [J]. European Heart Journal, 2024,45.DOI:10.1093/eurheartj/ehae666.2862.

[8] 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.

[9] 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.

[10] 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.

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.