Tirzepatid 15mg we yu de yuz

▎ Tirzepatid Strukchɔ

Sos: PubChem

Sikyud: . Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Lyu-Asp-Lys-Ile-Ala-Gln-{diasid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Fhe-Val-Gln-Trp-Lyu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Mɔlikul Fɔmula: C 225H 348N 48O68 Molekyula Weyt: 4813 g/mol CAS Nɔmba: 2023788-19-2 PubChem CID: 163285897, ɛn di ɔda wan dɛn Sinonim dɛn: Zepbound; Mounjaro we de na di wɔl

▎ Tirzepatid Risach

Wetin na di risach bakgrɔn fɔ Tirzepatid?

Tirzepatid na wan sintetik polipεptida drɔg. i divεlכpmεnt kכmכt frכm dip כndastandin fכ di limitεshכn dεm fכ di GLP-1 rεsεptכr agonist dεm we de naw fכ trit tayp 2 dayabεtis mεlitus (T2DM) εn fכ fat. pan ɔl we di GLP-1 riseptɔ agonist dɛn dɔn sho fayn fayn wok fɔ kɔntrol di glukɔs na di blɔd ɛn fɔ lɔs di wet, sayɛnsman dɛn dɔn si se dɛn aktiveshɔn fɔ di GIP riseptɔ rili wik, we de stɔp di tritmɛnt ifɛkt we di drɔgs dɛn gɛt. So, di risach ɛn divɛlɔpmɛnt tim dɔn mekɔp dɛn maynd fɔ mek wan nyu kayn drɔg we kin mek ɔl tu di GIPR ɛn GLP-1R aktiv wan tɛm, we dɛn aim fɔ ajɔst mɔ kɔmprɛhnsiv ɛn ifektiv blɔd glukɔs kɔntrol ɛn wet mɛnejɛmɛnt ^[1]..

We dɛn de du di risach ɛn divɛlɔpmɛnt, sayɛnsman dɛn dɔn du bɔku bɔku bɛsik risach stɔdi dɛn ɛn klinik trial dɛn. Insay di prɛklinik risach stej, dɛn bin evaluate di famakodaynamik prɔpati dɛm fɔ Tirzepatid gud gud wan tru animal ɛkspiriɛns, we dɛn chɛk in pɔtnɛshɛl fɔ kɔntrol blɔd glukɔs ɛn fɔ lɔs di wet. di risal dεm sho se i kin ridyus di blכd glukכs lεvεl bכku bכku wan na animal mכdel dεm εn i sho se i de du fayn fayn wan pan wet mεnejmεnt, we lay di fawndeshכn fכ klinik trial dεm we go kam afta dat.

Afta dat, di klinik trial stej inklud Faz I, II, ɛn III trayal dɛn. Di Faz I trayal men wan bin evalyu di sef, tolerabiliti, ɛn famakokinɛtik prɔpati dɛm fɔ di drɔg. Di rizɔlt sho se Tirzepatid bin gɛt gud sef ɛn tolɛrabiliti. Di Faz II trayal bin fכs εksplכr di efεktiv εn sef fכ difrεn doz dεm fכ Tirzepatid insay pasεnshכn dεm wit T2DM, fכs dεtermin in ifektiv doz rεnj. Di mɔs impɔtant Faz III klinik trayal dɛm, lɛk di SURPASS siriɔs stɔdi dɛm, involv bɔku bɔku pasɛnt dɛm wit T2DM. di risalts sho se Tirzepatid bin sכmtεm sכmtεm pas di GLP-1 rεsεptכr agonist dεm we bin de, lεk semaglutide, fכ ridyus di blכd glukכs εn wet, we gi strכng pruf fכ di makεt aplikεshכn fכ Tirzepatid ^[1]..

Wetin na di we aw Tirzepatid de wok?

Tirzepatid de lכs di glukכs na di bכdi tru mכtalman mεkanism dεm we de wok togeda. we i de aktibכt di GLP-1 rεsεpכta, Tirzepatid de biεn di GLP-1 rεsεpכta pan pankrεas β-sεl dεm, we de miks di akshכn fכ nεchכral GLP-1. GLP-1 na כmon we dεn prodyuz na di intestinal εn i implεnt fכ mεnten glukכs homכstasis. I kin mek insulin sεntez, sekreshכn, εn glukכs sεns, ridyus glukכn sekreshכn fכ mek yu sati, εn sכprεs di apεtit.

dis aktibכshכn kin mek insulin sekreshכn. insulin na di men haypoglycemic homon na di bodi, we kin mek di sεl dεm tek glukכs εn yuz am bכku, we de mek di glukכs lεvεl na di bכdi dכn. pan di sik pipul dεm we gεt T2DM, di insulin sekreshכn nכ de infεkt כ di sεl dεm in sεnsitiviti to insulin de dכn, we de mek di blכd glukכs go כp. bay we i de aktibכt di GLP-1 rεsεpכta, Tirzepatid de inkrεs insulin sekreshכn, we de εp fכ impruv di bכdi glukכs kכntrכl.

di sem tεm, di aktibכshכn fכ di GLP-1 rεsεpכta de inhεbit di rilis fכ glukagon bak. glukagon kin mek di glycogenolysis εn gluconeogenesis we yu de fast, we de mek di bכdi glukכs prodakshכn go כp. bay we i de inhibit di akshכn fכ glukagon, Tirzepatid de ridyus di sכs fכ di glukכs na di bכdi, we de kכntribyut fכ kכntrכl di glukכs na di bכdi ^[2]..

we i de aktibכt di GIP rεsεpכta, Tirzepatid de akt pan di GIP rεsεpכta wan tεm. afta i aktibכt, i kin εnhans insulin sεnsitiviti εn sekreshכn. di GIP risεptor de mεntal insay tisu dεm lεk pankrεas β-sεl dεm. afta di aktibכshכn, tru di transmishכn fכ di intasεlulyar signal path dεm, di insulin sekreshכn de inkrεs, εn di sεl in rεspכns to insulin de impruv, so dat de ridyus di glukכs na di bכdi mכr ifektiv wan.

Tirzepatid na fכs in klas dual glukagon lεk pεptida-1 εn glukכs-dipεndεnt insulinotropik polipεptida (GIP) analכg, we dεn apruv fכ trit big pipul dεm wit T2DM as adjunkt to it εn εksεsayz. Tirzepatid na sεntetik kεmikכl strכkchכ we de bays pan di GIP sikεns, we kכmכp fכ 39-amino asid pεptida. i de mek insulin sekreshכn bכku, i de ridyus glukכn we de kכmכt pan glukכs we dipεnd pan glukכs, i de lכs di fast εn afta it di bכdi glukכs lεvεl, i de mek di bכdi satis, i de ridyus di bכdi wet, εn i de delay di gεstrik εmpti. dis dual risεptor agonist ifekt de mek Tirzepatid mכr ifektiv pas singl GLP-1 rεsεpכta agonist dεm fכ protεkt insulin sekreshכn εn inhεbit glukagon rilis ^[2]..

Tirzepatid kin delay bak fɔ ɛmti di bɛlɛ ɛn i kin mek yu satisfay. i kin delay di gastric ɛmti, i kin mek di it fɔ de na di bɛlɛ lɔng ɛn i kin slo di absɔpshɔn rit fɔ di nyutriɛnt dɛn, so dat i kin mek di blɔd glukɔs go ɔp shap shap. insay nכn-klinik εn klinik stכdi dεm, di ifekt we Tirzepatid gεt pan gεstrik εmpti de kכmparabl wit di wan we GLP-1 rεsεptכr agonist dεm gεt. insay di it-induced obese mice, di digri we di gastric emptying delay bay Tirzepatid na di sem wit di wan we semaglutide de du, bכt dεn akyu inhibitory ifekt dεm ya de disappear afta 2 wiks we dεn trit am.

In patisipan dεm wit εn witout T2DM, wan tεm insay wik Tirzepatid (≥5 mg εn ≥4.5 mg, rispεktivli) delay gastric εmpti afta wan singl dכz. In hεlty patisipan dεm, di ifekt bin atεnuet afta mכltipכl dכz כf Tirzepatid כ dulaglutide (Urva S, 2020). pan di sem tεm, i kin akt bak pan di sεntri nεv sεstem, i kin mek i satis bכku, i kin mek i nכ want fכ it, εn i kin it. bay we i de kכntrכl di it we yu de it, i de εp indaykt fכ kכntrכl di blכd glukכs lεvεl, spεshal wan we fit fכ di fat prכblεm we kin kכmכt wit di sik pipul dεm we gεt T2DM bכku tεm, εn i de εp fכ impruv insulin rεsistεns εn di כvala mεtabolik stetכs ^[2]..

dεn fכnshכn se tirzepatid de inkrεs di lεvεl fכ adiponectin, we na adipocytokine we riliyt to insulin sεnsitiviti. we di adiponectin lεvεl inkrεs de εp fכ impruv insulin sεnsitiviti, we de mek di sεl dεm de rεspכnd to insulin mכr, so dat de tek εn yuz glukכs fayn fayn wan εn ridyus glukכs na di bכdi ^[2] . apat frכm dat, Tirzepatid kin impruv di lipid profayl bak εn i kin gεt pכtεnshal prכtektiv ifekt pan di kכdivaskyul hεlth. dεn pruv se tirzepatid ebul fכ impruv bכdi prεshכn, rεdכks lכw-dεnsiti lipoprotein (LDL) kכlestכl εn triglisεrayd ^[3] , we de sכpכt in kכmprεhεnsiv bεnεfit dεm fכ mεnejmεnt blכd glukכs.

Sos: PubMed ^{[5] we dɛn pul am.}

Risach we gɛt fɔ du wit dis

Efikεsi pan wεt mεnejmεnt pan pasεnshכn dεm we fat εn tayp 2 dayabεtis mεllitus

Bɔku klinik stɔdi dɛn dɔn kɔnfyus di signifyant ɛfifikɛshɔn fɔ Tirzepatid fɔ di manejmɛnt fɔ bɔdi wet pan pasɛnt dɛn we gɛt fat ɛn T2DM. Insay wan stɔdi we dɛn kɔl 'SURMOUNT-2', we na bin Faz 3, dabl-blaynd, randomized, plasɛbo-kɔntrol trial we dɛn du na sɛvin kɔntri dɛn. Adult (we ol ≥18 ia) wit bɔdi mas indeks (BMI) we na 27 kg/m² ɔ ay pas dat ɛn wan glycated hemoglobin (HbA2c) lɛvɛl we na 7 - 10% dɛn bin randomly asaynd fɔ gɛt wan tɛm ɛvri wik sabkyutan injɛkshɔn fɔ Tirzepatid (10 mg ɔ 15 mg) ɔ plasɛbo fɔ 72 wik.

Di risal sho se na wik 72, di pasɛnt we di wet lɔs na di Tirzepatid 10 mg ɛn 15 mg grup na bin -12.8% ɛn -14.7%, rispɛktvɔli, kɔmpia wit -3.2% na di plasɛbo grup. Di ɛstimat tritmɛnt difrɛns fɔ Tirzepatid 10 mg ɛn 15 mg kɔmpia wit di plesibo na bin -9.6 pasɛnt poɛnt ɛn -11.6 pasɛnt poɛnt, rispɛktvɔli, we ɔl tu na bin statystikal sifyukɛnt (p < 0.0001). pan tap dat, wan big pat pan di sik pipul dεm we de gεt Tirzepatid tritmεnt rich di thrεshold fכ lכs wet 5% כ mכr (79 - 83% vs 32%) ^[4]..

Insay di 'SURMOUNT-2' stɔdi, di beslayn avɛrej wet na bin 100.7 kg, di BMI na bin 36.1 kg/m², ɛn di HbA1 na bin 8.02%. Afta 72 wiks we dɛn trit am, Tirzepatid nɔ bin jɔs ridyus di bɔdi wet bad bad wan bɔt i bin gɛt fayn ɛfɛkt bak pan blɔd glukɔs kɔntrol ^[4]..

Improvement effect pan di nyuropathy we gɛt fɔ du wit dayabitis

ome stכdi dεn dכn pכynt se GLP1-RA dεm kin ridyus di risk fכ dimεnshכn pan pasεn dεm we gεt T2DM bay we dεn de impruv mεmכri, lan, εn כvakom di kכgnitiv impεryans. As dual GIP-RA/GLP-1RA, Tirzepatid bin stכdi in di nyuroblastoma sel layn (SHSY5Y) fכ in ifekt pan mak dεm fכ nyuronal growth (CREB εn BDNF), apoptosis (BAX/Bcl2 rεshכ), difrεns (pAkt, MAP2, GAP43, εn AGBL4), εn insulin rεsistεns (GLUT1, GLUT4, GLUT3, εn SORBS1).

di risal fכ di fכs tεm εnfaz di rol we Tirzepatid de ple fכ aktibכt di pAkt/CREB/BDNF path εn dכwnstrim signal kaskad, εn bak in nyuroprotεktiv efikכs. i sho bak se Tirzepatid bin ebul fכ kכntrכl di ifekt dεm we riliyt to haypa glycemia εn insulin rεsistεns na di nyuronal lεvεl. So, Tirzepatid kin impruv di nyurodijεnεreshכn we de kכz fכ haypa glycemia εn i kin כvakom nyuronal insulin rεsistεns, we de gi nyu insayt fכ impruv di nyuropathy we rilayt to dayabεtis ^[5]..

Risach prɔgrɛs fɔ trit tayp 2 dayabitis mɛlitus

Sɔm stɔdi dɛn dɔn sho se as nyu kayn haypoglycemic drɔg, Tirzepatid dɔn bi di fɔs dual GIP/GLP-1R agonist we dɛn dɔn gri fɔ trit dayabitis na Amɛrika. Dɛn dɔn kɔnfyus se i gɛt bɔku ifɛkt pan fɔ lɛ di blɔd glukɔs go dɔŋ ɛn fɔ ridyus di bɔdi wet pan bɔku big klinik trial dɛm, ɛn pruf de we sho se i gɛt bɔku pawa bak fɔ protɛkt di at ɛn di blɔd.

apat frכm dat, di kכnsεpt fכ sεntetik pεptida dεn dכn opin plεnti posisibul dεm we dεn nכ no fכ Tirzepatid. Trial we de go bifo (NCT04166773) ɛn pruf sho se i tan lɛk se na prɔmis drɔg pan fil dɛm lɛk nɔ-alkohol fat liva sik (NAFLD), rεnal protεkshɔn, ɛn nyuroprotεkshɔn ^[6]..

Lכng tεm ifekt dεm we tirzepatide gεt pan di kכdivaskyul hεlth

Tirzepatid kin ridyus di risk fɔ gɛt sik dɛn we de ambɔg di at ɛn di blɔd bay we i de mek pɔsin lɔs in wet. Wan stכdi bin εgzamεn di impak we Tirzepatid gεt pan fכ fat εn kכdivaskyul sik ivent dεm na Amɛrikan big pipul dεm (Wong ND, 2024). Di stεdi fכnshכn se pan Amεriכn big pipul dεm we fit fכ Tirzepatid tritmεnt, afta tritmεnt wit 15 mg Tirzepatid, dεn εstimat se 70.6% εn 56.7% pan di big pipul dεm bin gεt weit lכs ≥15% εn ≥20%, rispεktivli, we min se 58.8% ridyus pan di nכmba כf pipul dεm we fat.

Na di wan dɛm we nɔ gɛt kadyovaskyuɛl sik, di ɛstimat 10 ia kadiɔvaskyuɛl sik risk dɔn go dɔŋ frɔm 10.1% 'bifo tritmɛnt' to 7.7% 'afta tritmɛnt', we sho se absɔlɔb risk ridɔkshɔn fɔ 2.4% ɛn rilitiv risk ridɔkshɔn fɔ 23.6%, we min se 2 milyɔn kadiɔvaskyuɛl sik ivin dɛn kin dɔn insay 10 ia.

fכ kכnklushכn ,Tirzepatid na nכvel dual agonist fכ GIP εn GLP-1 rεsεpכta dεm, we gεt big sכmtin fכ di tritmεnt fכ T2DM εn fכ fat. i kin mek insulin sekreshכn mכr ifektiv, inhibit glukagon sekreshכn, prεsisli rεgulεt bכdi glukכs, rεdכks di risk fכ komplikεshכn, impruv di fכnshכn fכ pankrεas β-sεl dεm, εn delay di prכgreshכn fכ dayabitis. I gɛt ɛfɛkt bak we de protɛkt di at ɛn di blɔd sistɛm.

We dɛn de trit pipul dɛn we fat, i kin rili ridyus di it we dɛn de it, mek dɛn nɔ want fɔ it, i kin mek dɛn satis, ɛp di wan dɛn we fat fɔ lɛ dɛn nɔ gɛt bɔku bɔku bɔdi, ɛn i kin mek dɛn nɔ gɛt prɔblɛm dɛn we kin apin we dɛn fat pasmak. I kin mek bak di insulin rɛsistɛns ɛn lipid mɛtabolism bɛtɛ. Apat frɔm dat, i dɔn sho se i kin ebul fɔ trit sik dɛn we gɛt fɔ du wit mɛtabolik dizayd lɛk stiatohepatitis we nɔ de drink rɔm, slip apnia sindrom, ɛn at we nɔ de wok fayn. i kin impruv mכltipכl mεtabolik indikεtכ dεm wan tεm, we de gi mכr kכmprεhεnsiv tritmεnt plan.

Di injɛkshɔn we dɛn kin gi am wan tɛm insay di wik kin izi fɔ yuz ɛn i kin mek di sikman dɛn fala di tritmɛnt fayn fayn wan.

Bɔt di pɔsin we rayt di buk

Di tin dɛm we wi dɔn tɔk bɔt ɔp na ɔl di risach, ɛdit ɛn kɔmpilayt na Cocer Peptides.

Sayɛns Jɔnal Author

Dɔktɔ Wiliam T. Gavi na wan big masta sabi bukman ɛn risachman we gɛt fɔ du wit bɔku bɔku big big institiushɔn dɛn, lɛk di Yunivasiti ɔf Alabama na Bɛmingham, Aston Yunivasiti, ɛn di Bɛmingham Veterans Afɛj Mɛdikal Sɛnta. In akademik bakgrɔn ɛn in wok ɛkspiriɛns span bɔku difrɛn disiplin dɛn insay di mɛdikal ɛn sayɛns fild dɛn. Dɔktɔ Garvey dɔn mek bɔku kɔntribyushɔn to di fild dɛm fɔ ɛndokrinɔlɔji ɛn mɛtabolism, nyutrishɔn ɛn itɛttiks, bayɔkemistri ɛn mɔlikul bayoloji, ɛn bak jenɛral ɛn intanɛnt mɛrɛsin, wit patikyula fɔs pan di kadiovaskular sistɛm ɛn kadiɔlɔji. Bɔku pipul dɛn dɔn no ɛn ɔnɔ in wok, mɔ we dɛn kɔl am Highly Cited Researcher in di Cross-Field kategori fɔ ɔl tu di 2023 ɛn 2024, we sho di big impak ɛn inflɛns we in risach gɛt pan di brayt sayɛns kɔmyuniti.

Dכkta Garvey in risach intres εn εkspεriεns de εksεnd to difrεn aspek dεm fכ mεtabolik sik dεm εn dεn mεnejmεnt. I dɔn de wok tranga wan fɔ stɔdi bɔt dayabitis, fɔ fat, ɛn di prɔblɛm dɛn we gɛt fɔ du wit dɛn, ɛn i dɔn aim fɔ fɛn nyu tritmɛnt strateji ɛn fɔ mek di pɔsin gɛt bɛtɛ tin fɔ du. In wok inkɔmpas besik sayɛns risach, klinik trial, ɛn transleshɔnal stɔdi, we de briŋ di gap bitwin di tin dɛn we dɛn dɔn fɛn na lɛbɔretri ɛn di rial wɔl mɛdikal aplikeshɔn dɛn. Tru in bɔku risach, Dɔkta Garvey dɔn kɔntribyut fɔ ɔndastand mɔ bɔt di ɔndalayn mɛkanism dɛm fɔ mɛtabolik dizayd ɛn i dɔn ɛp fɔ shep klinik gaydlayn ɛn tritmɛnt protɔkɔl dɛm na di fild fɔ ɛndokrinɔlɔji ɛn mɛtabolism. Dɛn rayt Dɔktɔ Wiliam T. Gavi insay di rɛfrɛns fɔ saytayshɔn ^[4]..

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Nowak M, Nowak W, Grzeszczak W. Tirzepatid - wan dual GIP/GLP-1 rεsεptכr agonist - wan nyu antidiabetic drog wit pכtεnshal mεtabolik aktiviti in di tritmεnt fכ tayp 2 dayabεtis[J]. Ɛndokrinɔlɔjia Polska, 2022,73(4):745-755.DOI:10.5603/EP.a2022.0029.

[2] Nɔbɔdi nɔ no in nem. Tirzepatid: Na Dual Glucose-Dipεndεnt Insulinotropik Polipεptida εn Glucagon-Lεk Pεptid-1 Agonist fכ di Mεnejmεnt fכ Tayp 2 Dayabitis Mεlitus: Erratum.[J]. Amɛrikan Jɔnal fɔ Tɛrapi, 2023,30(3):e311.DOI:10.1097/MJT.0000000000001634.

[3] Fɔrzano I, Varzideh F, Avvisato R, ɛn ɔda pipul dɛn. Tirzepatid: Wan Sistɛm Ɔpdet[J]. Int ɛ rnash ɔ nal J ɔ rnal ɔ f Mɔlikul Sayns, 2022,23(23).DOI:10.3390/ijms232314631.

[4] Garvey WT, Frias JP, Jastreboff A. M., ɛn ɔda pipul dɛn. Tirzepatid wan tɛm ɛvri wik fɔ di tritmɛnt fɔ fat pan pipul dɛn we gɛt tayp 2 dayabitis (SURMOUNT-2): na dabl-blaynd, randomised, multicentre, placebo-controlled, phase 3 trial[J]. Lancet, 2023,402(10402):613-626.DOI:10.1016/S0140-6736(23)01200-X.

[5] Fontanella R. A., Ghosh P., Pɛsapane A, ɛn ɔda pipul dɛn. Tirzepatid de mek nyurodijεnεreshכn tru mכltipכl mכlikul path dεm[J]. J ɔ rnal ov Transleshɔnal Mɛdisin, 2024,22(1).DOI:10.1186/s12967-024-04927-z.

[6] Ma Z, Jin K, Yue M, ɛn ɔda pipul dɛn. Risach Prɔgrɛs pan di GIP/GLP-1 Risɛptɔ Kɔagonist Tirzepatid, wan Rising Sta insay Tayp 2 Dayabitis[J]. J ɔ rnal ɔ f Dayabitis Risach, 2023,2023.DOI: 10.1155/2023/5891532.

ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL DI INFƆMƐSHƆN DISƐMƐNƐSHƆN ƐN FƆ EDYUKESHƆN.  

Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.