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1 khoom (10Vials)
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▎ Tirzepatid 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 |
▎ Tirzepatid Kev Tshawb Fawb
Kev tshawb fawb keeb kwm ntawm Tirzepatid yog dab tsi?
Tirzepatid yog cov tshuaj hluavtaws polypeptide. 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 mob ntshav qab zib mellitus (T2DM) thiab rog rog. Txawm hais tias GLP-1 receptor agonists tau pom qhov ua tau zoo hauv kev tswj ntshav qabzib thiab poob phaus, cov kws tshawb fawb tau pom tias lawv qhov kev ua haujlwm ntawm GIP receptor yog qhov tsis muaj zog, uas txwv cov 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 ua rau ob qho tib si GIPR thiab GLP-1R ib txhij, txhawm rau ua kom 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, cov kws tshawb fawb tau ua ntau qhov kev tshawb fawb txog kev tshawb fawb thiab kev sim tshuaj. Nyob rau hauv lub preclinical kev tshawb fawb theem, lub pharmacodynamic zog ntawm Tirzepatid tau soj ntsuam xyuas los ntawm cov tsiaj thwmsim, xyuas nws cov peev xwm nyob rau hauv cov ntshav qabzib tswj thiab poob phaus. Cov txiaj ntsig tau pom tias nws tuaj yeem txo cov ntshav qabzib ntau hauv cov qauv tsiaj thiab ua kom pom kev ua tau zoo hauv kev tswj qhov hnyav, tso lub hauv paus rau kev sim tshuaj tom ntej.
Tom qab ntawd, qhov kev sim tshuaj ntsuam xyuas suav nrog Theem I, II, thiab III kev sim. Theem I mus sib hais mas ntsuam xyuas kev nyab xeeb, kam rau ua, thiab pharmacokinetic zog ntawm cov tshuaj. Cov txiaj ntsig tau qhia tias Tirzepatid muaj kev nyab xeeb zoo thiab ua haujlwm ntev. Theem II sim ntxiv tshawb xyuas qhov ua tau zoo thiab kev nyab xeeb ntawm cov koob tshuaj sib txawv ntawm Tirzepatid hauv cov neeg mob T2DM, ua ntej txiav txim siab nws cov koob tshuaj zoo. Qhov tseem ceeb tshaj plaws Phase III kev sim tshuaj, xws li SURPASS series ntawm kev tshawb fawb, koom nrog ntau tus neeg mob T2DM. Cov txiaj ntsig tau pom tias Tirzepatid tau zoo dua rau GLP-1 receptor agonists uas twb muaj lawm, xws li semaglutide, hauv kev txo cov ntshav qabzib thiab qhov hnyav, muab pov thawj muaj zog rau kev lag luam daim ntawv thov ntawm Tirzepatid [1].
Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm Tirzepatid?
Tirzepatid txo cov ntshav qabzib los ntawm ntau lub tshuab ua haujlwm ua ke. Thaum ua kom lub GLP-1 receptor, Tirzepatid khi rau GLP-1 receptor ntawm pancreatic β-hlwb, ua raws li qhov kev txiav txim 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. Nws tuaj yeem txhawb kev tsim cov tshuaj insulin, zais cia, thiab ntsuas ntshav qabzib, txo qis glucagon secretion los txhawb satiety, thiab txo qis qab los noj mov.
Qhov kev ua kom muaj zog no tuaj yeem txhawb kev tsim cov tshuaj insulin. Insulin yog lub ntsiab hypoglycemic cov tshuaj hormones hauv lub cev, uas tuaj yeem txhim kho kev noj qab haus huv thiab kev siv cov piam thaj los ntawm cov hlwb, yog li txo cov ntshav qabzib. Hauv cov neeg mob uas muaj T2DM, insulin secretion tsis txaus lossis cell rhiab heev rau insulin txo, ua rau cov ntshav qabzib nce siab. Los ntawm kev ua kom lub GLP-1 receptor, Tirzepatid nce insulin secretion, uas pab txhim kho cov ntshav qabzib tswj.
Nyob rau tib lub sijhawm, kev ua haujlwm ntawm GLP-1 receptor kuj inhibits qhov tso tawm ntawm glucagon. Glucagon feem ntau txhawb nqa glycogenolysis thiab gluconeogenesis thaum yoo mov, ua kom cov ntshav qabzib ntau ntxiv. Los ntawm inhibiting qhov kev txiav txim ntawm glucagon, Tirzepatid ntxiv txo cov ntshav qabzib, pab tswj ntshav qabzib [2].
Thaum ua rau GIP receptor, Tirzepatid ua rau GIP receptor ib txhij. 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 haujlwm, los ntawm kev sib kis ntawm intracellular signaling pathways, insulin secretion yog nce, thiab lub cell lub teb rau insulin yog txhim kho, yog li ntawd zoo dua txo cov ntshav qabzib.
Tirzepatid yog thawj-hauv-chav kawm dual glucagon-zoo li peptide-1 thiab cov piam thaj-dependent insulinotropic polypeptide (GIP) analog, tau pom zoo rau kev kho mob ntawm cov neeg laus nrog T2DM raws li kev noj haus thiab kev tawm dag zog. Tirzepatid yog cov qauv tshuaj hluavtaws raws li GIP ib ntus, muaj li ntawm 39-amino acid peptide. Nws tsub kom insulin secretion, txo glucagon tso tawm raws li cov piam thaj-dependant, txo qis kev yoo mov thiab postprandial ntshav qabzib theem, txhawb kev satiety, txo lub cev qhov hnyav, thiab qeeb plab hnyuv. Qhov no dual receptor agonist nyhuv ua rau Tirzepatid zoo dua li ib leeg GLP-1 receptor agonists hauv kev txhawb nqa insulin secretion thiab inhibiting glucagon tso tawm [2].
Tirzepatid kuj tseem tuaj yeem ncua lub plab zom mov thiab ua kom satiety. Nws tuaj yeem ncua lub plab zom mov, ua kom lub sijhawm nyob ntawm cov zaub mov hauv lub plab thiab ua kom qeeb ntawm kev nqus ntawm cov as-ham, yog li tsis txhob muaj qhov nce siab hauv cov ntshav qabzib tom qab. Hauv cov kev tshawb fawb uas tsis yog kev kho mob thiab kev kho mob, cov nyhuv ntawm Tirzepatid ntawm lub plab khoob yog piv rau GLP-1 receptor agonists. Hauv kev noj zaub mov kom cov nas rog rog, qhov ntsuas ntawm lub plab zom mov qeeb los ntawm Tirzepatid zoo ib yam li cov semaglutide, tab sis cov teebmeem inhibitory no ploj tom qab 2 lub lis piam kho.
Hauv cov neeg koom nrog thiab tsis muaj T2DM, Tirzepatid ib zaug ib lub lim tiam (≥5 mg thiab ≥4.5 mg, ntsig txog) ncua kev ua pa ntawm plab tom qab ib koob tshuaj. Hauv cov neeg koom nrog noj qab haus huv, cov nyhuv tau txo qis tom qab ntau koob tshuaj Tirzepatid lossis dulaglutide (Urva S, 2020). Nyob rau tib lub sijhawm, nws tuaj yeem ua rau lub hauv nruab nrab lub paj hlwb, ua kom satiety, txo qab los noj mov, thiab noj zaub mov. Los ntawm kev tswj hwm kev noj zaub mov, nws tsis ncaj qha los tswj cov ntshav qabzib, tshwj xeeb tshaj yog tsim nyog rau cov teeb meem rog rog feem ntau nrog cov neeg mob T2DM, thiab pab txhim kho insulin tsis kam thiab tag nrho cov txheej txheem metabolic [2].
Tirzepatid tau pom tias nce qib ntawm adiponectin, ib qho adipocytokine cuam tshuam rau insulin rhiab heev. Kev nce qib ntawm adiponectin pab txhim kho insulin rhiab heev, ua rau cov hlwb ua rau cov tshuaj insulin ntau dua, yog li kev noj qab haus huv zoo dua thiab txo cov ntshav qabzib [2] . Tsis tas li ntawd, Tirzepatid tuaj yeem txhim kho cov lipid profile thiab muaj peev xwm tiv thaiv kab mob plawv. Tirzepatid tau raug pov thawj tias tuaj yeem txhim kho cov ntshav siab, txo qis lipoprotein tsawg (LDL) cov roj cholesterol thiab triglycerides [3] , ntxiv dag zog rau nws cov txiaj ntsig zoo hauv kev tswj ntshav qabzib.
Source: PubMed [5]
Kev tshawb fawb ntsig txog
Kev ua tau zoo ntawm kev tswj qhov hnyav hauv cov neeg mob rog rog thiab hom 2 mob ntshav qab zib mellitus
Ntau qhov kev tshawb fawb soj ntsuam tau lees paub qhov ua tau zoo ntawm Tirzepatid hauv kev tswj hwm lub cev hnyav hauv cov neeg mob rog thiab T2DM. Hauv kev tshawb fawb hu ua 'SURMOUNT-2', uas yog Theem 3, ob qhov muag tsis pom kev, randomized, cov tshuaj placebo tswj kev 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) qib ntawm 7 - 10% tau muab tso rau kom tau txais kev txhaj tshuaj subcutaneous ib lim piam ntawm Tirzepatid (10 mg lossis 15 mg) 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 Tirzepatid 10 mg thiab 15 mg pawg yog -12.8% thiab -14.7%, feem, piv nrog -3.2% hauv pawg placebo. Kev kwv yees qhov sib txawv ntawm kev kho mob ntawm Tirzepatid 10 mg thiab 15 mg piv nrog cov placebo yog -9.6 feem pua cov ntsiab lus thiab -11.6 feem pua cov ntsiab lus, feem, ob qho tib si tseem ceeb (p <0.0001). Tsis tas li ntawd, feem ntau ntawm cov neeg mob tau txais kev kho mob Tirzepatid tau mus txog qhov hnyav ntawm 5% lossis ntau dua (79 - 83% vs 32%) [4].
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, Tirzepatid tsis tsuas yog txo lub cev hnyav xwb tab sis kuj muaj txiaj ntsig zoo rau kev tswj ntshav qabzib [4].
Kev txhim kho cov txiaj ntsig ntawm ntshav qab zib ntsig txog neuropathy
ome kev tshawb fawb tau taw qhia tias GLP1-RAs tuaj yeem txo qhov kev pheej hmoo ntawm dementia hauv cov neeg mob T2DM los ntawm kev txhim kho kev nco, kev kawm, thiab kov yeej kev puas hlwb. Raws li ib tug dual GIP-RA / GLP-1RA, Tirzepatid tau kawm nyob rau hauv lub neuroblastoma cell kab (SHSY5Y) rau nws cov teebmeem ntawm cov cim ntawm neuronal kev loj hlob (CREB thiab BDNF), apoptosis (BAX / Bcl2 ratio), sib txawv (pAkt, MAP2, GAP43, thiab AGBL4), thiab insulin resistance (SGLUT1, GLUT1, BS1, GLUT1, thiab insulin resistance).
Cov txiaj ntsig thawj zaug tau hais txog lub luag haujlwm ntawm Tirzepatid hauv kev ua kom lub pAkt / CREB / BDNF txoj hauv kev thiab qis qis qis qis qis, nrog rau nws cov txiaj ntsig neuroprotective. Nws kuj tau qhia tias Tirzepatid muaj peev xwm tiv thaiv cov teebmeem cuam tshuam nrog hyperglycemia thiab insulin tsis kam ntawm qib neuronal. Yog li, Tirzepatid tuaj yeem txhim kho cov neurodegeneration los ntawm hyperglycemia thiab kov yeej cov tshuaj insulin tsis kam, muab cov kev nkag siab tshiab rau kev txhim kho cov ntshav qab zib neuropathy [5].
Kev tshawb nrhiav kev nce qib hauv kev kho mob ntshav qab zib hom 2
Qee cov kev tshawb fawb tau taw qhia tias yog hom tshuaj hypoglycemic tshiab, Tirzepatid tau dhau los ua thawj tus neeg thib ob GIP / GLP-1R agonist pom zoo rau kev kho mob ntshav qab zib hauv Tebchaws Meskas. Nws tau raug lees paub tias muaj cov txiaj ntsig tseem ceeb ntawm kev txo cov ntshav qabzib thiab txo lub cev hnyav hauv ntau qhov kev sim tshuaj loj, thiab muaj pov thawj qhia 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 Tirzepatid. Kev sim tsis tu ncua (NCT04166773) thiab cov pov thawj qhia tias nws zoo li yog cov tshuaj cog lus hauv thaj chaw xws li kab mob tsis muaj dej cawv fatty siab (NAFLD), kev tiv thaiv lub raum, thiab kev tiv thaiv neuroprotection [6].
Kev cuam tshuam ntev ntawm tirzepatide rau kev noj qab haus huv ntawm lub plawv
Tirzepatid 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 Tirzepatid rau kev rog rog thiab kab mob plawv hauv Asmeskas cov neeg laus (Wong ND, 2024). Txoj kev tshawb no pom tias ntawm cov neeg laus Asmeskas tsim nyog tau txais kev kho mob Tirzepatid, tom qab kev kho mob nrog 15 mg ntawm Tirzepatid, nws tau kwv yees tias 70.6% thiab 56.7% ntawm cov neeg laus muaj qhov hnyav poob ntawm ≥15% thiab ≥20%, feem, uas txhais tau tias txo qis ntawm 58.8% ntawm cov neeg rog.
Ntawm cov uas tsis muaj kab mob plawv, kwv yees li 10-xyoo kab mob plawv txo qis los ntawm 10.1% 'ua ntej kho' mus rau 7.7% 'tom qab kev kho', uas qhia txog qhov kev pheej hmoo txo qis ntawm 2.4% thiab tus txheeb ze pheej hmoo txo qis ntawm 23.6%, uas txhais tau hais tias 2 lab cov kab mob plawv hauv 1 xyoo.
Hauv kev xaus, Tirzepatid yog ib qho tshiab dual agonist ntawm GIP thiab GLP-1 receptors, uas yog qhov tseem ceeb hauv kev kho mob ntawm T2DM thiab rog 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 mob ntshav qab zib. Nws kuj muaj kev tiv thaiv zoo ntawm cov hlab plawv.
Hauv kev kho mob rog rog, nws tuaj yeem txo cov khoom noj kom tsawg, txo qis qab los noj mov, ua kom satiety, pab cov neeg mob 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 tau pom tias muaj peev xwm hauv kev kho mob ntawm cov kab mob metabolic cuam tshuam xws li tsis muaj cawv steatohepatitis, pw tsaug zog apnea syndrome, thiab lub plawv tsis ua haujlwm. Nws tuaj yeem txhim kho ntau yam kev ntsuas metabolic ib txhij, muab cov phiaj xwm kev kho mob ntau dua.
Nws txoj kev txhaj tshuaj ib zaug ib lub lim tiam yog qhov yooj yim rau siv thiab tuaj yeem txhim kho cov neeg mob txoj kev kho raws li txoj cai.
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 muaj txiaj ntsig, tshwj xeeb yog hu ua Tus Kws Tshaj Lij Tshaj Lij Tshaj Lij Tshaj Lij 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 thiab kev txawj ntse txuas mus rau ntau yam ntawm cov kab mob metabolic thiab lawv txoj kev tswj hwm. Nws tau koom tes nrog kev kawm txog ntshav qab zib mellitus, 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 tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [4].
