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1 khoom (10Vials)
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▎ Tirzepatide Structure
Source: PubChem |
Ib ntus: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser-NH2 Molecular Formula: C 225H 348N 48O68 Molecular Luj: 4813 g / mol CAS Nr .: 2023788-19-2 PubChem CID: 163285897 Synonyms: Zepbound; Mounjaro |
▎ Kev Tshawb Fawb Tirzepatide
Kev tshawb fawb keeb kwm ntawm Tirzepatide yog dab tsi?
Tirzepatide yog ib qho tshuaj hluavtaws polypeptide, thiab nws txoj kev loj hlob yog los ntawm kev nkag siab tob txog cov kev txwv ntawm GLP-1 receptor agonists uas twb muaj lawm hauv kev kho mob ntawm hom 2 metabolism mellitus thiab rog rog. Txawm hais tias GLP-1 receptor agonists twb tau ua haujlwm zoo hauv kev tswj cov ntshav qabzib thiab poob phaus, cov kws tshawb fawb tau pom tias thaum lawv qhib GLP-1 receptor, lawv cov nyhuv ua rau ntawm GIP receptor yog qhov tsis muaj zog, uas rau qee qhov txwv qhov kev kho mob ntawm cov tshuaj. Yog li ntawd, pab neeg tshawb fawb thiab kev tsim kho tau cog lus los tsim ib hom tshuaj tshiab uas tuaj yeem qhib ob qho tib si GIPR thiab GLP-1R ib txhij, nyob rau hauv kev cia siab ntawm kev ua tiav ntau dua thiab muaj txiaj ntsig zoo ntshav qabzib tswj thiab tswj qhov hnyav [1] .
Thaum lub sij hawm kev tshawb fawb thiab kev loj hlob ntawm Tirzepatide, cov kws tshawb fawb tau ua ntau yam kev tshawb fawb thiab kev sim tshuaj. Ua ntej ntawm tag nrho cov, nyob rau hauv lub preclinical kev tshawb fawb theem, lub pharmacodynamic yam ntxwv ntawm Tirzepatide tau soj ntsuam heev los ntawm cov tsiaj thwmsim, thiab nws muaj peev xwm nyob rau hauv cov ntshav qabzib tswj thiab yuag poob. Cov txiaj ntsig tau pom tias Tirzepatide tuaj yeem txo cov ntshav qabzib ntau hauv cov qauv tsiaj thiab kuj ua tau zoo hauv kev tswj qhov hnyav. Cov kev tshawb pom zoo no tau tsim lub hauv paus ruaj khov rau cov kev sim tshuaj tom ntej.
Tom qab ntawd, Tirzepatide tau nkag mus rau theem kev sim tshuaj, suav nrog theem I, II, thiab III kev sim. Hauv theem kuv sim, kev nyab xeeb, kev zam, thiab cov yam ntxwv ntawm cov tshuaj pharmacokinetic feem ntau tau soj ntsuam, thiab cov txiaj ntsig tau pom tias Tirzepatide muaj kev nyab xeeb zoo thiab ua haujlwm ntev. Kev sim theem II tau tshawb fawb ntxiv txog kev ua tau zoo thiab kev nyab xeeb ntawm cov koob tshuaj sib txawv ntawm Tirzepatide hauv cov neeg mob uas muaj hom 2 metabolism mellitus, thiab ua ntej txiav txim siab nws cov koob tshuaj zoo. Qhov tseem ceeb tshaj plaws ntawm theem III kev sim tshuaj, xws li SURPASS series ntawm kev tshawb fawb, tau them rau ntau tus neeg mob uas muaj hom 2 metabolism mellitus. Cov txiaj ntsig tau pom tias Tirzepatide tau zoo dua rau GLP-1 receptor agonists uas twb muaj lawm, xws li semaglutide, txo cov ntshav qabzib thiab qhov hnyav. Qhov kev tshwm sim no tau muab pov thawj muaj zog txhawb rau kev lag luam daim ntawv thov ntawm Tirzepatide [1].
Tirzepatide yog polypeptide muaj li ntawm 39 amino acids, nyob rau hauv uas ib tug neeg amino acids tau raug hloov kho los txhim kho nws stability thiab kev ua tau zoo. Cov qauv tsim tshwj xeeb no ua rau Tirzepatide sib xyaw ua ke cov teebmeem ntawm ob qho tshuaj hormones incretin, GIP thiab GLP-1, rau hauv ib qho molecule, thiab qhib cov tshuaj hormones koom nrog hauv kev tswj ntshav qabzib los ntawm kev ua haujlwm ntawm ob lub tswv yim. Tshwj xeeb, Tirzepatide tuaj yeem ua rau ntawm lub txiav thiab lub hauv nruab nrab lub paj hlwb. Ntawm ib sab, nws txhawb kev tsim cov tshuaj insulin thiab inhibits glucagon tso tawm, yog li txo cov ntshav qabzib zoo; ntawm qhov tod tes, los ntawm kev ncua lub plab khoob thiab ua kom satiety, nws txo qis qab los noj mov, thiab yog li ua tiav kev tswj hwm qhov hnyav. Qhov kev ua haujlwm thib ob no muab Tirzepatide tshwj xeeb zoo hauv kev kho mob ntawm hom 2 metabolism mellitus thiab rog, muab cov neeg mob nrog kev xaiv kev kho mob ntau dua [1].
Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm Tirzepatide?
Tirzepatide txo qis cov ntshav qabzib los ntawm ntau lub tswv yim ua haujlwm ua ke, raws li hauv qab no: Ua kom lub GLP-1 receptor: Tirzepatide khi rau GLP-1 receptor ntawm pancreatic β hlwb, ua raws li cov txiaj ntsig ntawm ntuj GLP-1. GLP-1 yog ib yam tshuaj uas tsim nyob rau hauv txoj hnyuv thiab tseem ceeb heev rau kev tswj cov piam thaj homeostasis 2. Nws tuaj yeem txhawb nqa cov tshuaj insulin synthesis, insulin secretion, thiab qabzib sensing, thiab txo glucagon secretion los txhawb satiety thiab inhibit qab los noj mov 2.
Qhov kev ua kom muaj zog no tuaj yeem txhawb kev tsim cov tshuaj insulin. Insulin yog lub luag haujlwm tseem ceeb hauv cov ntshav qabzib cov tshuaj hormones hauv lub cev, uas tuaj yeem ua rau kom nce ntxiv thiab siv cov piam thaj los ntawm cov hlwb, yog li txo cov ntshav qabzib. Hauv cov neeg mob uas muaj hom 2 metabolism hauv cov ntshav, insulin secretion tsis txaus lossis cov hlwb rhiab heev rau insulin raug txo, ua rau cov ntshav qabzib nce ntxiv. Tirzepatide nce insulin secretion los ntawm activating GLP-1 receptor, uas pab txhim kho cov ntshav qabzib tswj. Nyob rau tib lub sijhawm, kev ua haujlwm ntawm GLP-1 receptor tuaj yeem cuam tshuam qhov tso tawm ntawm glucagon. Glucagon feem ntau txhawb nqa glycogenolysis thiab gluconeogenesis hauv lub xeev yoo mov, ua kom cov ntshav qabzib ntau ntxiv. Los ntawm inhibiting cov nyhuv ntawm glucagon, Tirzepatide ntxiv txo cov ntshav qabzib, uas pab tswj cov ntshav qabzib [2] (Anonymous, 2023).
Ua kom GIP receptor: Tirzepatide ua rau GIP receptor tib lub sijhawm. Tom qab ua kom tiav, nws tuaj yeem txhim kho kev nkag siab ntawm insulin thiab tso tawm. GIP receptor feem ntau muaj nyob hauv cov ntaub so ntswg xws li pancreatic β hlwb. Tom qab ua kom muaj zog, los ntawm kev ua ntawm txoj kev taw qhia intracellular, insulin secretion yog nce, thiab cov hlwb cov lus teb rau insulin zoo tuaj, yog li txo cov ntshav qabzib ntau dua 2. Tirzepatide yog thawj-hauv-chav dual glucagon-zoo li peptide-1 thiab cov piam thaj-dependent insulinotropic polypeptide (GIP) ntawm cov neeg laus cov kev kho mob hom 2. ntxiv rau kev noj haus thiab kev tawm dag zog 2. Tirzepatide yog cov qauv tshuaj hluavtaws raws li GIP ib ntus, muaj li ntawm 39-amino acid peptide. Nws nce insulin secretion, txo qhov tso tawm ntawm glucagon hauv cov piam thaj hauv cov ntshav, txo qis kev yoo mov thiab postprandial ntshav qabzib qib, txhawb kev satiety, txo qhov hnyav, thiab qeeb plab hnyuv 2.
Qhov no dual receptor agonist nyhuv ua rau Tirzepatide zoo dua los txhawb cov insulin secretion thiab inhibiting glucagon tso tawm dua ib zaug GLP-1 receptor agonists [2].
Kev ncua lub plab zom mov thiab ua kom satiety: Tirzepatide tuaj yeem ncua lub plab zom mov, ua kom lub sijhawm nyob ntawm cov zaub mov hauv plab, txo qis qhov nqus ntawm cov as-ham, thiab yog li zam kom tsis txhob muaj qhov nce ntxiv hauv cov ntshav qabzib tom qab. Hauv kev tshawb fawb txog kev kho mob thiab kev kho mob, cov nyhuv ntawm Tirzepatide ntawm lub plab khoob yog piv rau GLP-1 receptor agonists. Hauv kev noj zaub mov kom cov nas rog rog, qhov ntsuas ntawm qhov qeeb ntawm lub plab khoob los ntawm Tirzepatide zoo ib yam li cov semaglutide, tab sis cov kev cuam tshuam hnyav no ploj tom qab 2 lub lis piam ntawm kev kho mob. Hauv cov neeg koom nrog thiab tsis muaj hom 2 metabolism mellitus, Tirzepatide ib zaug ib lub lim tiam (≥5 thiab ≥4.5mg, feem) ncua kev ua pa ntawm plab tom qab ib koob tshuaj. Hauv cov neeg koom nrog noj qab haus huv, cov nyhuv no tau txo qis tom qab ntau koob tshuaj Tirzepatide lossis dulaglutide [3] .
Nyob rau tib lub sijhawm, nws tuaj yeem ua rau lub hauv nruab nrab lub paj hlwb, ua kom satiety, thiab txo qis qab los noj mov thiab noj zaub mov. Los ntawm kev tswj hwm kev noj zaub mov, nws tsis ncaj qha pab tswj cov ntshav qabzib, tshwj xeeb tshaj yog tsim nyog rau cov teeb meem rog rog feem ntau nrog cov neeg mob uas muaj hom 2 metabolism, thiab pab txhim kho insulin tsis kam thiab tag nrho cov txheej txheem metabolic [2].
Txhim kho cov tshuaj insulin rhiab heev thiab lipid metabolism: Tirzepatide tau pom tias nce qib ntawm adiponectin, uas yog adipocytokine cuam tshuam nrog insulin rhiab heev. Kev nce qib ntawm adiponectin pab txhim kho insulin rhiab heev, ua rau cov hlwb rhiab heev rau insulin, thiab yog li siv tau zoo dua thiab siv cov piam thaj, txo cov ntshav qabzib [2].
Tsis tas li ntawd, Tirzepatide tuaj yeem txhim kho cov lipid profile thiab muaj peev xwm tiv thaiv kab mob plawv. Tirzepatide tau raug pov thawj tias tuaj yeem txhim kho ntshav siab, txo qis lipoprotein tsawg (LDL) cov roj cholesterol thiab triglycerides [4] .Qhov no ntxiv txhawb nws cov txiaj ntsig zoo hauv kev tswj ntshav qabzib.
Kev tshawb fawb ntsig txog
Kev ua tau zoo ntawm kev tswj qhov hnyav hauv cov neeg mob rog rog thiab hom 2 metabolism mellitus:
Ntau qhov kev tshawb fawb soj ntsuam tau lees paub qhov kev poob ceeb thawj tseem ceeb: Hauv kev tshawb fawb hu ua 'SURMOUNT-2', qhov kev sim no yog theem 3, ob qhov muag tsis pom kev, randomized, placebo-tswj sim ua nyob rau hauv xya lub teb chaws. Cov neeg laus (hnub nyoog ≥18 xyoo) nrog lub cev qhov hnyav (BMI) ntawm 27 kg / m² los yog siab dua thiab glycated hemoglobin (HbA₁c) ntawm 7 - 10% tau muab tso ua ke kom tau txais kev txhaj tshuaj subcutaneous ib zaug ntawm Tirzepatide (10mg lossis 15mg) lossis placebo rau 72 lub lis piam. Cov txiaj ntsig tau pom tias nyob rau lub lim tiam 72, qhov feem pua ntawm qhov poob phaus hauv Tirzepatide 10mg thiab 15mg pawg yog -12.8% thiab -14.7%, feem, thaum nyob hauv pawg placebo yog -3.2%. Kev kwv yees qhov sib txawv ntawm kev kho mob ntawm Tirzepatide 10mg thiab 15mg piv nrog cov placebo yog -9.6 feem pua cov ntsiab lus thiab -11.6 feem pua ntawm cov ntsiab lus, feem, ob qho tib si yog qhov tseem ceeb (p＜0.0001). Tsis tas li ntawd, ntau tus neeg mob kho nrog Tirzepatide tau nce mus txog qhov hnyav ntawm 5% lossis ntau dua (79 - 83% vs 32%) [5] (Garvey WT, 2023). Hauv qhov kev tshawb fawb 'SURMOUNT-2', qhov nruab nrab qhov hnyav yog 100.7 kg, BMI yog 36.1 kg / m² thiab HbA₁c yog 8.02%. Tom qab 72 lub lis piam ntawm kev kho mob, Tirzepatide tsis tsuas yog txo qhov hnyav xwb tab sis kuj ua lub luag haujlwm zoo hauv kev tswj ntshav qabzib [5].
Kev txhim kho cov txiaj ntsig ntawm cov metabolism cuam tshuam txog neuropathy:
Qee cov kev tshawb fawb tau taw qhia tias glucagon-zoo li peptide 1 receptor agonists (GLP1-RAs) tuaj yeem txo qhov kev pheej hmoo ntawm dementia hauv cov neeg mob uas muaj hom 2 metabolism hauv kev txhim kho kev nco, kev kawm, thiab kov yeej kev puas hlwb. Raws li ib tug dual qabzib-dependent insulin polypeptide receptor agonist (GIP-RA) / GLP-1RA, Tirzepatide tau kawm txog nws cov teebmeem ntawm cov cim ntawm kev loj hlob ntawm neuronal (CREB thiab BDNF), apoptosis (BAX / Bcl2 ratio), kev sib txawv (pAkt, MAP2, GAP43, thiab AGGLUT1, thiab insulin, SORBS1) hauv kab mob neuroblastoma cell (SHSY5Y). Cov txiaj ntsig thawj zaug tau hais txog lub luag haujlwm ntawm Tirzepatide hauv kev ua kom lub pAkt / CREB / BDNF txoj hauv kev thiab cov kev taw qhia qis qis, nrog rau nws qhov ua tau zoo hauv kev tiv thaiv neuroprotection. Nws kuj tau pom tias Tirzepatide tuaj yeem tiv thaiv cov teebmeem cuam tshuam nrog hyperglycemia thiab insulin tsis kam ntawm qib neuronal. Yog li, Tirzepatide tuaj yeem txhim kho cov neurodegeneration tshwm sim los ntawm hyperglycemia thiab kov yeej cov tshuaj insulin tsis kam, muab cov kev nkag siab tshiab rau kev txhim kho cov metabolism hauv neuropathy [6] .
Kev tshawb nrhiav kev nce qib hauv kev kho mob ntawm hom 2 metabolism mellitus:
Qee qhov kev tshawb fawb tau taw qhia tias Tirzepatide, uas yog ib hom tshuaj hypoglycemic tshiab, tau dhau los ua thawj ob GIP / GLP-1R agonist tau pom zoo rau kev kho cov metabolism hauv Tebchaws Meskas. Nws tau raug lees paub tias muaj cov ntshav qabzib txo qis thiab qhov hnyav poob hauv ntau qhov kev sim tshuaj loj, thiab muaj pov thawj tias nws tseem muaj peev xwm tiv thaiv kab mob plawv. Tsis tas li ntawd, lub tswv yim ntawm hluavtaws peptides tau qhib ntau yam tsis paub txog Tirzepatide. Kev sim tsis tu ncua (NCT04166773) thiab cov pov thawj qhia tias nws zoo li yog cov tshuaj cog lus hauv thaj chaw ntawm cov kab mob tsis muaj dej cawv fatty siab (NAFLD), lub raum thiab neuroprotection, thiab lwm yam . [7].
Cov teebmeem ntev ntawm T irzepatide rau kev noj qab haus huv ntawm lub plawv:
Tirzepatide tuaj yeem txo qhov kev pheej hmoo ntawm cov kab mob plawv los ntawm kev txhawb nqa qhov hnyav. Ib txoj kev tshawb fawb tau tshuaj xyuas qhov cuam tshuam ntawm Tirzepatide rau kev rog rog thiab cov kab mob plawv hauv Asmeskas cov neeg laus [8] . Txoj kev tshawb fawb pom tias ntawm cov neeg laus Asmeskas tau txais kev kho mob Tirzepatide, tom qab kev kho mob nrog 15mg ntawm Tirzepatide, nws tau kwv yees tias 70.6% thiab 56.7% ntawm cov neeg laus muaj qhov hnyav ntawm ≥25% ntawm cov neeg uas muaj feem cuam tshuam, thiab cov neeg laus muaj qhov hnyav ntawm ≥ 15% ntawm cov neeg laus. los ntawm 58.8%. Hauv cov neeg uas tsis muaj kab mob plawv, kwv yees li 10-xyoo txoj kev pheej hmoo ntawm cov kab mob plawv tau txo qis los ntawm 10.1% ua ntej kev kho mob mus rau 7.7% tom qab kev kho mob, uas cuam tshuam qhov kev pheej hmoo ntawm kev txo qis ntawm 2.4% thiab tus txheeb ze yuav txo tau ntawm 23.6%, uas txhais tau hais tias 2 lab tus kab mob plawv tuaj yeem tiv thaiv tsis pub dhau 10 xyoo.
Hauv kev xaus, Tirzepatide yog ib qho tshiab dual agonist ntawm GIP thiab GLP-1 receptors thiab tseem ceeb heev hauv kev kho mob ntawm hom 2 metabolism mellitus thiab rog. Nws tuaj yeem txhawb kev tsim cov tshuaj insulin ntau dua, inhibit glucagon secretion, tswj cov ntshav qabzib, txo cov kev pheej hmoo ntawm cov teeb meem, txhim kho kev ua haujlwm ntawm pancreatic β hlwb, thiab ncua kev loj hlob ntawm cov metabolism. Nws kuj muaj kev tiv thaiv zoo ntawm cov hlab plawv. Hauv kev kho mob rog rog, nws tuaj yeem txo cov zaub mov kom tsawg, txo qis qab los noj mov, ua kom satiety, pab cov neeg rog rog rog, thiab txo cov kev pheej hmoo ntawm kev rog rog. Nws kuj tseem tuaj yeem txhim kho insulin tsis kam thiab lipid metabolism. Tsis tas li ntawd, nws qhia tau hais tias muaj peev xwm hauv kev kho mob ntawm cov kab mob metabolic abnormality xws li cov kab mob uas tsis yog cawv steatohepatitis, pw tsaug zog apnea syndrome, thiab lub plawv tsis ua hauj lwm, thiab tuaj yeem txhim kho ntau yam kev ntsuas metabolic, muab kev kho mob ntau dua. Nws txoj kev tswj hwm kev txhaj tshuaj ib zaug ib lub lim tiam yog yooj yim siv thiab tuaj yeem txhim kho cov neeg mob kev ua raws cai. Los ntawm kev tswj cov ntshav qabzib thiab qhov hnyav thiab txo qhov kev pheej hmoo ntawm cov teeb meem, cov neeg mob lub cev tuaj yeem txhim kho tau zoo, lawv lub peev xwm ua haujlwm txhua hnub thiab lub neej zoo tuaj yeem txhim kho, lawv txoj kev ntseeg siab ntawm kev tswj hwm tus kab mob tuaj yeem nce ntxiv, lawv lub nra hnyav tuaj yeem txo, thiab lawv cov kev sib raug zoo tuaj yeem txhim kho.
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
Dr. William T. Garvey yog ib tug kws tshaj lij thiab kws tshawb fawb koom nrog ntau lub tsev kawm ntawv muaj koob npe, suav nrog University of Alabama ntawm Birmingham, Aston University, thiab Birmingham Veterans Affairs Medical Center. Nws keeb kwm kev kawm thiab kev paub dhau los nthuav dav ntau yam kev qhuab qhia hauv kev kho mob thiab kev tshawb fawb. Dr. Garvey tau ua haujlwm tseem ceeb rau kev ua haujlwm ntawm endocrinology thiab metabolism, khoom noj khoom haus thiab kev noj haus, biochemistry thiab molecular biology, nrog rau cov tshuaj dav dav thiab sab hauv, nrog rau kev tsom mus rau cov hlab plawv thiab cov hlab plawv. Nws txoj haujlwm tau txais kev lees paub dav dav thiab tau txais txiaj ntsig, tshwj xeeb tshaj yog raug hu ua Tus Kws Tshawb Fawb Tshaj Lij Tshaj Lij Tshaj Lij rau ob qho tib si 2023 thiab 2024, qhia txog qhov cuam tshuam loj heev thiab cuam tshuam ntawm nws txoj kev tshawb fawb hauv zej zog kev tshawb fawb dav dav.
Dr. Garvey txoj kev tshawb fawb txog kev txaus siab thiab kev txawj ntse txuas mus rau ntau yam ntawm cov kab mob metabolic thiab lawv txoj kev tswj hwm. Nws tau koom nrog hauv kev kawm txog cov metabolism hauv kev rog, rog rog, thiab lawv cov teeb meem cuam tshuam, txhawm rau nthuav tawm cov tswv yim kho tshiab thiab txhim kho cov txiaj ntsig ntawm tus neeg mob. Nws txoj haujlwm suav nrog kev tshawb fawb txog kev tshawb fawb, kev sim tshuaj kho mob, thiab kev tshawb nrhiav kev txhais lus, cuam tshuam qhov sib txawv ntawm kev kuaj pom thiab daim ntawv thov kev kho mob tiag tiag. Los ntawm nws txoj kev tshawb fawb dav dav, Dr. Garvey tau pab txhawb kom nkag siab tob txog cov txheej txheem hauv qab ntawm cov kab mob metabolic thiab tau pab kho cov txheej txheem kho mob thiab cov txheej txheem kho mob hauv thaj chaw endocrinology thiab cov metabolism. Dr. William T. Garvey muaj npe nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [5].
