Retatrutide (GLP-3) 20 mg

▎ Retatrutide 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 Cov ntsiab lus: LY3437943

▎ Kev Tshawb Nrhiav Retatrutide

Kev tshawb fawb keeb kwm ntawm Retatrutide yog dab tsi?

Kev tshawb fawb keeb kwm yav dhau los ntawm Retatrutide yog ze ze rau cov teeb meem loj thoob ntiaj teb ntawm kev rog thiab metabolism, nrog rau cov kev txwv ntawm cov tshuaj kho mob uas twb muaj lawm: rog rog thiab metabolism ua rau muaj kev hem thawj rau pej xeem kev noj qab haus huv, nrog rau cov neeg rog rog hauv ntiaj teb tau kwv yees mus txog 4.005 billion los ntawm 2035 thiab tus naj npawb ntawm cov neeg mob metabolic nce mus txog 592 lab, ua rau muaj kev noj qab haus huv thoob ntiaj teb. Multi-target receptor agonist peptides tau tshwm sim los ua ib qho kev daws teeb meem, muaj peev xwm tiv thaiv kev rog rog, kho cov metabolism, thiab zam kom tsis txhob muaj kev phom sij ntawm cov tshuaj uas twb muaj lawm, ua rau lawv muaj kev sib txawv ntawm kev rog rog thiab kev kho mob metabolism.

Lub mechanism ntawm kev txiav txim ntawm Retatrutide yog dab tsi?

Regulating zog metabolism los ntawm multi-receptor activation

Retatrutide yog triple receptor agonist tsom rau cov piam thaj-dependent insulinotropic polypeptide receptor (GIPR), glucagon-zoo li peptide-1 receptor (GLP-1R), thiab glucagon receptor (GCGR). Nws ib txhij activates peb receptors, tswj lub zog metabolism los ntawm ntau txoj kev.

GIPR agonist ua haujlwm: 

GIP yog ib qho tshuaj insulin-secreting hauv plab hnyuv secreted los ntawm plab hnyuv K hlwb thiab tso tawm tom qab noj mov. Retatrutide activates GIPR, txhawb kev tsim cov tshuaj insulin, ua kom cov tshuaj insulin rhiab heev, thiab yog li pab lub cev nqus tau zoo dua thiab siv cov piam thaj, yog li txo cov ntshav qabzib. Tsis tas li ntawd, GIP tuaj yeem cuam tshuam cov roj metabolism los ntawm kev tswj hwm adipocyte muaj nuj nqi thiab txo cov rog rog ^[1].

GLP-1R agonist kev ua haujlwm: 

GLP-1 yog peptide hormone secreted los ntawm txoj hnyuv L hlwb. Tom qab ua kom GLP-1R, Retatrutide tsim ntau yam txiaj ntsig. Nws tuaj yeem txhawb kev tsim cov tshuaj insulin hauv cov piam thaj hauv cov ntshav, yog li txo cov ntshav qab zib. Nws tuaj yeem ncua lub plab zom mov, ua kom satiety, thiab txo cov khoom noj. GLP-1R agonism kuj tseem tuaj yeem ua rau lub hauv nruab nrab lub paj hlwb, tswj kev qab los noj mov thiab lub zog sib npaug, yog li pab kom poob phaus ^[2].

GCGR agonist cuam tshuam: 

Glucagon feem ntau ua rau cov ntshav qabzib nce ntxiv, tab sis raws li kev cuam tshuam ntawm Retatrutide, GCGR agonism ua rau muaj qhov sib txawv. Nws txhawb nqa glycogenolysis thiab gluconeogenesis hauv daim siab. Raws li kev sib xyaw ua ke ntawm Retatrutide, lub cev tsis muaj kev nce qib hauv cov ntshav qabzib yooj yim tab sis hloov kho lub zog metabolism kom nce rog, yog li ua tiav qhov poob phaus thiab txhim kho cov metabolism. GCGR agonism kuj tseem tuaj yeem cuam tshuam rau lub siab lipid metabolism, txo cov rog hauv siab ^[3].

Cov txiaj ntsig ntawm Kev Mob Ntshav Qab Zib Txog Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv

Los ntawm tib lub sijhawm ua haujlwm ntawm peb qhov receptors, Retatrutide cuam tshuam ntau yam metabolism hauv lub cev.

Kev tswj cov ntshav qabzib: 

Los ntawm kev ua kom GIPR thiab GLP-1R los txhawb kev tso cov tshuaj insulin, thiab tswj GCGR kom tsim nyog, Retatrutide tuaj yeem txo cov ntshav qabzib. Nws cov nyhuv hypoglycemic tau tshaj tawm thaum cov ntshav qabzib nce siab, thaum nws tsis zoo li ua rau hypoglycemia thaum cov ntshav qabzib zoo li qub, uas muaj txiaj ntsig zoo rau kev tswj ntshav qabzib hauv cov neeg mob ntshav qab zib ^[4].

Kev tswj qhov hnyav: 

Retatrutide qhia tau hais tias muaj txiaj ntsig zoo hauv kev tswj qhov hnyav. Los ntawm kev ua kom GLP-1R, nws ua rau lub plab zom mov qeeb, ua kom satiety, thiab txo cov zaub mov noj; los ntawm kev tswj cov roj metabolism, nws txhawb kev rog rog thiab kev siv hluav taws xob, yog li ua tiav qhov hnyav. Kev sim tshuaj ntsuam xyuas tau pom tias cov neeg mob rog rog lossis rog rog tau kho nrog Retatrutide muaj kev poob ceeb thawj hauv ib lub sijhawm ^[5,6].

Lipid txoj cai: 

Kev kho Retatrutide txhim kho cov neeg mob 'lipid profile. Nws txo qis triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), thiab tsawg-density lipoprotein cholesterol (VLDL-C), thaum tseem tswj hwm apolipoproteins, xws li txo qis apolipoprotein B (apoB) thiab apolipoprotein C-III (apoarticles nrog rau qib III) atherosclerosis thiab txhawb kev mob plawv ^[7].

Txhim kho hepatic lipid metabolism: 

Rau cov neeg mob uas tsis yog-alcoholic fatty siab kab mob (NAFLD) cuam tshuam nrog metabolic dysfunction, Retatrutide ho txo ​​cov roj hepatic. Hauv kev sim tshuaj ntsuam xyuas, cov neeg mob kho nrog ntau koob tshuaj ntawm Retatrutide tau pom tias muaj cov txheeb ze txo qis hauv daim siab rog cov ntsiab lus piv rau cov hauv paus ntsiab lus, qhia tias Retatrutide muaj cov txiaj ntsig zoo ntawm cov roj metabolism hauv lub siab, uas muaj txiaj ntsig zoo rau kev txhim kho daim siab ua haujlwm ^[3].

Daim duab 1 Retatrutide cov txheej txheem ntawm kev ua ^[8].

Cov ntawv thov ntawm Retatrutide yog dab tsi?

Kev kho mob rog rog: 

Kev rog rog dhau los ua qhov teeb meem tseem ceeb hauv ntiaj teb kev noj qab haus huv, cuam tshuam nrog kev pib thiab kev loj hlob ntawm ntau yam kab mob. Retatrutide tau pom tias muaj txiaj ntsig zoo hauv kev kho mob rog. Cov neeg mob rog rog kho nrog Retatrutide tau ntsib qhov txo qis hauv lub cev hnyav. Hauv 48-lub lim tiam Phase 2 kev tshawb fawb kev rog, cov neeg mob kho nrog 8mg thiab 12mg ntawm Retatrutide tau ntsib qhov hnyav ntawm 22.8% thiab 24.2%, feem. Hauv lwm Theem 2 ob-dig muag, randomized, placebo-tswj sim, cov neeg mob nyob rau hauv ntau pab pawg tau ntsib qhov sib txawv ntawm qhov hnyav ntawm 24 lub lis piam thiab 48 lub lis piam. Cov pab pawg 12mg tau ua tiav qhov hnyav ntawm 24.2% ntawm 48 lub lis piam, thaum pawg placebo tsuas pom qhov txo qis ntawm -2.1%. Retatrutide zoo txo ​​lub cev hnyav hauv cov neeg mob rog, muab cov cuab yeej tshiab thiab muaj zog rau kev kho mob rog. Retatrutide therapy rau kev rog rog tsis tsuas yog txo lub cev hnyav xwb tab sis kuj tseem tuaj yeem txhim kho lwm yam kev noj qab haus huv cuam tshuam nrog kev rog, xws li txo cov kev ntxhov siab ntawm kev sib koom tes thiab txo cov tsos mob ntawm kev rog rog los ntawm kev poob phaus; Kev txo qhov hnyav kuj tseem tuaj yeem pab txhim kho kev rog rog xws li pw tsaug zog apnea ^[3,6].

Hom 2 kev kho mob metabolism: 

Hom 2 metabolic yog ib qho teeb meem ntawm cov kab mob metabolic uas tshwm sim los ntawm cov tshuaj insulin tsis kam thiab tsis txaus cov tshuaj insulin. Retatrutide muaj peev xwm siv tau rau hauv kev kho mob ntawm hom 2 metabolism. Nws txhawb kev tsim cov tshuaj insulin los ntawm kev ua kom lub GLP-1 receptor, txhim kho insulin tsis kam, thiab txo cov ntshav qabzib. Nws cov txiaj ntsig txo qhov hnyav kuj tseem pab txhim kho tus mob ntawm cov neeg mob ntshav qab zib hom 2, vim tias rog rog yog qhov tseem ceeb ntawm cov metabolism hauv hom 2, thiab kev poob phaus tuaj yeem txhim kho insulin rhiab heev, ntxiv kev pab tswj ntshav qabzib. Hauv kev tshawb fawb txog cov neeg mob uas muaj hom 2 metabolism, Retatrutide ua rau poob ceeb thawj thiab qhov tseem ceeb txo qis hauv qib hemoglobin A1c (HbA1c), nrog HbA1c txo los ntawm 1.64% piv rau cov placebo. Qhov no qhia tau hais tias Retatrutide tsis tsuas yog tswj cov ntshav qab zib kom zoo tab sis kuj txhim kho tag nrho cov mob ntawm cov neeg mob uas muaj hom 2 metabolism los ntawm ntau lub tswv yim, suav nrog kev poob phaus, yog li txhim kho lawv lub neej zoo ^[6].

Tsis-alcoholic fatty siab kab mob (NAFLD) kev kho mob: 

NAFLD yog ib qho metabolic stress-induced lub siab raug mob zoo sib xws nrog insulin tsis kam thiab genetic susceptibility, encompassing ib spectrum ntawm tej yam kev mob xws li tsis-alcoholic yooj yim fatty siab, tsis-alcoholic steatohepatitis, thiab lwm yam cirrhosis. Retatrutide qhia tau hais tias muaj peev xwm zoo hauv kev kho NAFLD. Hauv kev sib piv, ob qhov muag tsis pom kev, kev sim tshuaj placebo nrog cov neeg koom nrog cov kab mob metabolic tsis ua haujlwm cuam tshuam nrog cov kab mob siab rog thiab lub siab rog cov ntsiab lus ≥10%, ntawm 24 lub lis piam, qhov sib txawv nruab nrab ntawm lub siab cov rog cov ntsiab lus los ntawm lub hauv paus tseem ceeb sib txawv thoob plaws Retatrutide koob tshuaj pawg: -81.4% hauv pawg 8mg 20% thiab 8mg. hauv pawg placebo. Qhov no qhia tau hais tias Retatrutide tuaj yeem txo cov rog hauv siab, uas yog qhov tseem ceeb rau kev txhim kho daim siab pathology ntawm NAFLD cov neeg mob. Nws tuav cov lus cog tseg raws li qhov kev xaiv kho tshiab rau NAFLD, uas tuaj yeem ua rau muaj kab mob qeeb zuj zus thiab txo qhov kev pheej hmoo ntawm cov teeb meem loj xws li cirrhosis ^[3].

Xaus

Retatrutide qhia tau hais tias muaj peev xwm los txhim kho cov kab mob hepatic pathological ntawm NAFLD cov neeg mob, ua haujlwm los ntawm ntau lub tswv yim suav nrog kev tswj hwm lub zog metabolism, txhim kho insulin tsis kam, tiv thaiv cov teebmeem, thiab hloov kho lipid metabolism.

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 ib tus kws tshaj lij uas nws txoj haujlwm tau txuas nrog ntau lub tsev muaj koob npe, suav nrog University of Texas Southwestern Medical Center, University of Texas Dallas, thiab Canadian VIGOR Center. Nws txoj kev tshawb fawb nthuav dav ntau yam xws li Endocrinology & Diabetes, General & Internal Medicine, Cardiovascular System & Cardiology, Pharmacology & Pharmacy, thiab Kev Tshawb Fawb & Kev Siv Tshuaj. Nws qhov txiaj ntsig zoo tshaj plaws rau kev kawm hauv zej zog tau ua rau nws tau txais kev lees paub thoob plaws, raws li tau pom los ntawm nws qhov kev xaiv rov ua dua li 'Tus Kws Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Plaws hauv Kev Kho Mob' los ntawm 2017 txog 2024, qhia txog nws txoj haujlwm tseem ceeb thiab muaj txiaj ntsig zoo hauv kev tshawb fawb 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] Brzozowska P, Frańczuk A, Nowińska B, et al. Retatrutide - kev hloov pauv tsis ntev los no tau tsim GLP agonist - cov ntaub ntawv tshuaj xyuas [J]. Zoo hauv Kev Ua Si, 2024.DOI: 10.12775/qs.2024.15.52125.

[2] Doggrell S A. Retatrutide qhia kev cog lus hauv kev rog (thiab hom 2 metabolism)[J]. Cov Lus Qhia Txog Kev Tshawb Fawb Txog Tshuaj, 2023,32(11): 997-1001.DOI: 10.1080/13543784.2023.2283020.

[3] Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist Retatrutide rau metabolic dysfunction-associated steatotic daim siab kab mob: ib theem randomized 2a sim [J]. Xwm Txheej, 2024,30:2037-2048.DOI:10.1038/s41591-024-03018-2.

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

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

[7] Nicholls S, Pirro V, Lin Y, et al. Triple-hormone receptor agonist Retatrutide txhim kho lipoprotein thiab apolipoprotein profiles hauv cov neeg koom nrog rog lossis rog [J]. European Heart Journal, 2024,45(1):666-1501.DOI:10.1093/eurheartj/ehae666.1501.

[8] Katsi V, Koutsopoulos G, Fragoulis C, et al. Retatrutide-A Game Changer in Obesity Pharmacotherapy: Biomolecules [Z]. 2025: 15.DOI: 10.3390/biom15060796.

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.