Tirzepatid 15 mg

▎ Ọdịdị Tirzepatid

Isi mmalite: PubChem

Usoro: 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-Pro-Ser-NH2 Ụdị mkpụrụ ndụ: C 225H 348N 48O68 Ibu ibu: 4813 g/mol Nọmba CAS: 2023788-19-2 PubChem CID: 163285897 Ụdị okwu: Zepbound; Mounjaro

▎ Nyocha Tirzepatid

Gịnị bụ ndabere nyocha nke Tirzepatid?

Tirzepatid bụ ọgwụ polypeptide sịntetik. Mmepe ya sitere na nghọta miri emi nke oke nke GLP-1 agonists nnabata nke dị na ọgwụgwọ ụdị ọrịa shuga mellitus 2 (T2DM) na oke ibu. Ọ bụ ezie na ndị na-anabata GLP-1 egosila ezigbo arụmọrụ na njikwa glucose ọbara na mbelata ibu, ndị ọkà mmụta sayensị achọpụtala na ịgbalite onye na-anabata GIP adịghị ike, nke na-egbochi mmetụta ọgwụgwọ nke ọgwụ. Ya mere, ndị otu nyocha na mmepe agbaala mbọ n'ịmepụta ụdị ọgwụ ọhụrụ nke nwere ike ịgbalite ma GIPR na GLP-1R n'otu oge, na-achọ inweta njikwa glucose ọbara zuru oke ma dị irè na njikwa ibu ^[1]..

N'oge usoro nyocha na mmepe mmepe, ndị ọkà mmụta sayensị emeela ọnụ ọgụgụ dị ukwuu nke nchọpụta nchọpụta bụ isi na ule ụlọ ọgwụ. N'ime usoro nyocha nke izizi, a na-enyocha akụrụngwa ọgwụ ọgwụ nke Tirzepatid nke ọma site na nnwale anụmanụ, na-enyocha ikike ya na njikwa glucose ọbara na mbelata ibu. Nsonaazụ gosiri na ọ nwere ike belata ọkwa glucose ọbara n'ụzọ dị ukwuu n'ụdị anụmanụ ma gosipụta arụmọrụ dị mma na njikwa ibu, na-atọ ntọala maka ule ụlọ ọgwụ na-esote.

N'ikpeazụ, usoro nnwale ụlọ ọgwụ gụnyere ule nke Phase I, II, na III. Nnwale nke usoro nke mbụ tụlere nchekwa, nnabata, na akụrụngwa ọgwụ ọgwụ. Nsonaazụ gosiri na Tirzepatid nwere ezigbo nchekwa na nnabata. Nnwale oge nke Abụọ nyochara ịdị irè na nchekwa nke ọgwụ Tirzepatid dị iche iche n'ime ndị ọrịa nwere T2DM, na-ebu ụzọ chọpụta oke dose ya dị irè. Ọnwụnwa ụlọ ọgwụ kachasị mkpa nke Atọ III, dị ka usoro ọmụmụ SURPASS, metụtara ọnụ ọgụgụ buru ibu nke ndị ọrịa nwere T2DM. Nsonaazụ gosiri na Tirzepatid dị elu karịa GLP-1 agonists ndị na-anabata ihe dị ugbu a, dị ka semaglutide, na-ebelata glucose ọbara na ịdị arọ, na-enye ihe akaebe siri ike maka ngwa ahịa Tirzepatid ^[1]..

Kedu ihe bụ usoro nke Tirzepatid?

Tirzepatid na-ebelata glucose ọbara site na ọtụtụ usoro na-arụkọ ọrụ ọnụ. Mgbe ị na-arụ ọrụ onye na-anabata GLP-1, Tirzepatid na-ejikọta ya na GLP-1 onye na-anabata ya na mkpụrụ ndụ β-pancreatic, na-eṅomi omume nke GLP-1 eke. GLP-1 bụ homonụ nke emepụtara n'ime eriri afọ ma dị oke mkpa maka idowe glucose homeostasis. Ọ nwere ike ịkwalite njikọ insulin, nzuzo, na nghọta glucose, belata ihe nzuzo glucagon iji kwalite satiety, ma gbochie agụụ.

Nrụ ọrụ a nwere ike ịkwalite mmepụta insulin. Insulin bụ isi homonụ hypoglycemic dị na ahụ, nke nwere ike ịbawanye nnabata na ojiji nke glucose site na mkpụrụ ndụ, si otú ahụ belata ọkwa glucose ọbara. N'ime ndị ọrịa nwere T2DM, mmepụta insulin ezughi oke ma ọ bụ ikike sel na insulin na-ebelata, na-eduga n'ịbawanye glucose ọbara. Site na ịgbalite GLP-1 nnabata, Tirzepatid na-abawanye mmepụta insulin, nke na-enyere aka melite njikwa glucose ọbara.

N'otu oge ahụ, ịgbalite GLP-1 nnabata na-egbochikwa mwepụta nke glucagon. Glucagon na-akwalitekarị glycogenolysis na gluconeogenesis n'oge ibu ọnụ, na-abawanye mmepụta glucose ọbara. Site na igbochi ọrụ glucagon, Tirzepatid na-ebelata isi iyi nke glucose ọbara, na-enye aka na njikwa glucose ọbara ^[2]..

~!phoenix_var104!~

Tirzepatid bụ nke mbụ na klas nke abụọ glucagon-dị ka peptide-1 na glucose-based insulinotropic polypeptide (GIP) analog, nke akwadoro maka ọgwụgwọ ndị okenye nwere T2DM dị ka ihe mgbakwunye nri na mmega ahụ. Tirzepatid bụ usoro kemịkalụ sịntetịt dabere na usoro GIP, nke nwere peptide 39-amino acid mejupụtara. Ọ na-abawanye mmepụta insulin, na-ebelata mwepụta glucagon n'ụzọ dabere na glucose, na-ebelata ibu ọnụ na ọkwa glucose ọbara mgbe nri gasịrị, na-akwalite satiety, na-ebelata ibu ahụ, na-egbu oge ịpụpụ afọ. Mmetụta agonist onye na-anabata ihe abụọ a na-eme Tirzepatid dị irè karịa otu GLP-1 agonists na-anabata ya n'ịkwalite mmepụta insulin na igbochi ntọhapụ glucagon ^[2]..

Tirzepatid nwekwara ike igbu oge mkpofu afọ ma na-abawanye satiety. Ọ nwere ike igbu oge ịwụsa afọ, na-agbatị oge obibi nke nri n'ime afọ ma na-ebelata ọnụego nnabata nke nri, si otú a na-ezere ịrị elu nke glucose ọbara postprandial. N'ime ọmụmụ ihe na-abụghị nke ụlọ ọgwụ na ụlọ ọgwụ, mmetụta Tirzepatid na mkpofu gastric dị ka nke GLP-1 agonists na-anabata ya. N'ime oke oke oke nri kpatara nri, ogo igbu oge nke afọ nke Tirzepatid yiri nke semaglutide, mana mmetụta mgbochi ndị a na-apụ n'anya mgbe izu abụọ gachara ọgwụgwọ.

N'ime ndị na-eso ya na ndị na-enweghị T2DM, Tirzepatid otu ugboro kwa izu (≥5 mg na ≥4.5 mg, n'otu n'otu) na-egbu oge mkpochapụ afọ mgbe otu ọgwụ gasịrị. N'ime ndị sonyere ahụike, a na-ebelata mmetụta ahụ mgbe ọtụtụ doses nke Tirzepatid ma ọ bụ dulaglue etiti, na-abawanye satiety, ibelata agụụ, na iri nri. Site n'ịchịkwa ihe oriri, ọ na-enyere aka ịchịkwa ọkwa glucose ọbara n'ụzọ na-apụtaghị ìhè, karịsịa maka nsogbu oke ibu nke ndị ọrịa nwere T2DM na-esonyere ya, ma na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke ^[2]..

Achọpụtala Tirzepatid na-abawanye ọkwa nke adiponectin, adipocytokine metụtara mmetụta insulin. Mmụba nke ọkwa adiponectin na-enyere aka imeziwanye mmetụta insulin, na-eme ka mkpụrụ ndụ na-anabata insulin, si otú a na-ewere nke ọma na iji glucose na-ebelata glucose ọbara ^[2] . Na mgbakwunye, Tirzepatid nwekwara ike imeziwanye profaịlụ lipid ma nwee mmetụta nchebe na ahụike obi. E gosipụtara Tirzepatid na ọ nwere ike imeziwanye ọbara mgbali elu, belata obere lipoprotein (LDL) cholesterol na triglycerides ^[3] , na-akwadokwu uru ya na njikwa glucose ọbara.

Isi mmalite: PubMed ^[5]

Nnyocha metụtara ya

Ịdị irè na njikwa ibu na ndị ọrịa nwere oke ibu na ụdị ọrịa shuga mellitus nke 2

Ọtụtụ ọmụmụ ụlọ ọgwụ ekwenyela na uru Tirzepatid dị na njikwa arọ ahụ na ndị ọrịa nwere oke ibu na T2DM. N'ime ọmụmụ nke aha ya bụ 'SURMOUNT-2', nke bụ usoro nke atọ, kpuru ìsì abụọ, nke enweghị usoro, ebe a na-achịkwa placebo na mba asaa. Ndị okenye (ndị dị afọ ≥18) nwere ọnụọgụ anụ ahụ (BMI) nke 27 kg / m² ma ọ bụ karịa na ọkwa haemoglobin glycated (HbA₁c) nke 7-10% na-enyeghị usoro ịnata injections subcutaneous nke Tirzepatid otu ugboro kwa izu (10 mg ma ọ bụ 15 mg) ma ọ bụ placebo maka izu 72.

Nsonaazụ gosiri na n'ime izu 72, pasent nke ibu ibu na Tirzepatid 10 mg na 15 mg otu bụ -12.8% na -14.7%, n'otu n'otu, ma e jiri ya tụnyere -3.2% na placebo otu. Atụmatụ ọgwụgwọ dị iche iche nke Tirzepatid 10 mg na 15 mg ma e jiri ya tụnyere placebo bụ -9.6 pasent na -11.6 pasent, n'otu n'otu, ha abụọ dị ịrịba ama (p <0.0001). Na mgbakwunye, ọnụ ọgụgụ ka ukwuu nke ndị ọrịa na-anata ọgwụgwọ Tirzepatid ruru n'ókè nke mbelata ibu nke 5% ma ọ bụ karịa (79 - 83% vs 32%) ^[4].

N'ime ọmụmụ 'SURMOUNT-2', nkezi ịdị arọ nke ntọala bụ 100.7 kg, BMI bụ 36.1 kg/m², na HbA₁c bụ 8.02%. Mgbe izu iri asaa na abụọ nke ọgwụgwọ gasịrị, Tirzepatid abụghị naanị ibelata ibu ahụ nke ukwuu kamakwa ọ nwere mmetụta dị mma na njikwa glucose ọbara ^..

Mmetụta dị mma na neuropathy metụtara ọrịa shuga

ome ọmụmụ egosila na GLP1-RA nwere ike ibelata ihe ize ndụ nke ịda mbà n'obi na ndị ọrịa nwere T2DM site na imeziwanye ebe nchekwa, mmụta, na imeri adịghị ike nghọta. Dị ka ihe abụọ GIP-RA / GLP-1RA, Tirzepatid mụrụ na neuroblastoma cell line (SHSY5Y) maka mmetụta ya na nrịbama nke uto neuronal (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), ọdịiche (pAkt, MAP2, GAP43, na AGBL4), na insulin resistance (GBSLUT1).

Nsonaazụ maka oge mbụ kwusiri ike na ọrụ Tirzepatid n'ịgbalite ụzọ pAkt/CREB/BDNF na mgbago mgbago mgbago mgbago, yana nrụpụta neuroprotective ya. O gosikwara na Tirzepatid nwere ike igbochi mmetụta ndị metụtara hyperglycemia na nguzogide insulin na ọkwa neuronal. Ya mere, Tirzepatid nwere ike imeziwanye neurodegeneration nke hyperglycemia kpatara ma merie nguzogide insulin neuronal, na-enye nghọta ọhụrụ maka mmelite nke neuropathy metụtara ọrịa shuga ^[5]..

Ọganihu nyocha na ọgwụgwọ ụdị ọrịa shuga mellitus nke 2

Ụfọdụ nnyocha egosila na dị ka ụdị ọgwụ hypoglycemic ọhụrụ, Tirzepatid abụrụla onye mbụ GIP/GLP-1R agonist kwadoro maka ọgwụgwọ ọrịa shuga na United States. Ekwenyere na ọ nwere mmetụta dị ịrịba ama na mbelata glucose ọbara na ibelata ibu ahụ n'ọtụtụ nnukwu ule ụlọ ọgwụ, na enwere ihe akaebe na-egosi na ọ nwekwara ikike dị ukwuu na nchebe obi.

Na mgbakwunye, echiche nke peptides sịntetik emeghela ọtụtụ ohere amaghị maka Tirzepatid. Nnwale na-aga n'ihu (NCT04166773) na ihe akaebe na-egosi na ọ dị ka ọ bụ ọgwụ na-ekwe nkwa na mpaghara dịka ọrịa imeju na-adịghị egbu egbu (NAFLD), nchebe gbasara akụrụ, na neuroprotection ^[6].

Mmetụta ogologo oge nke tirzepatide na ahụike obi

Tirzepatid nwere ike ibelata ihe ize ndụ nke ọrịa obi site n'ịkwalite ibu ibu. Otu nnyocha nyochara mmetụta Tirzepatid na oke ibu na ọrịa obi na ọrịa obi na ndị okenye America (Wong ND, 2024). Nnyocha ahụ chọpụtara na n'etiti ndị okenye America tozuru oke maka ọgwụgwọ Tirzepatid, mgbe ọgwụgwọ na 15 mg nke Tirzepatid gasịrị, e mere atụmatụ na 70.6% na 56.7% nke ndị okenye nwere oke ibu nke ≥15% na ≥20%, n'otu n'otu, nke pụtara mbelata 58.8% na ọnụ ọgụgụ ndị buru oke ibu.

N'ime ndị na-enweghị ọrịa obi, ihe ize ndụ nke ọrịa obi afọ 10 e mere atụmatụ na-ebelata site na 10.1% 'tupu ọgwụgwọ' ruo 7.7% 'mgbe ọgwụgwọ gasịrị', na-egosipụta mbelata ihe ize ndụ zuru oke nke 2.4% na mbelata ihe ize ndụ nke 23.6%, nke pụtara na enwere ike igbochi ihe omume ọrịa obi 2 nde n'ime afọ 10.

Na mmechi, Tirzepatid bụ akwụkwọ akụkọ dual agonist nke GIP na GLP-1 ndị na-anabata ya, nke dị oke mkpa na ọgwụgwọ T2DM na oke ibu. Ọ nwere ike ịkwalite mmepụta insulin nke ọma, na-egbochi nzuzo nke glucagon, na-ahazi glucose ọbara nke ọma, belata ihe ize ndụ nke nsogbu, melite ọrụ nke mkpụrụ ndụ β-pancreatic, na-egbu oge ọganihu nke ọrịa shuga. Ọ nwekwara mmetụta nchebe na usoro obi.

N'ịgwọ oke ibu, ọ nwere ike ibelata oriri oriri nke ọma, ibelata agụụ, ịbawanye afọ ojuju, nyere ndị ọrịa buru ibu aka ifelata, ma belata ihe ize ndụ nke nsogbu ndị metụtara oke ibu. Ọ nwekwara ike melite nguzogide insulin na metabolism lipid. Tụkwasị na nke ahụ, o gosila ikike n'ịgwọ ọrịa ndị metụtara nsogbu metabolic dị ka steatohepatitis na-adịghị egbu egbu, ọrịa apnea ụra, na nkụda obi. Ọ nwere ike melite ọtụtụ ihe ngosi metabolic n'otu oge, na-enye atụmatụ ọgwụgwọ zuru oke.

Usoro ịgba ntụtụ ya otu ugboro kwa izu dị mma iji ma nwee ike melite nnabata ọgwụgwọ ndị ọrịa.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Dr. William T. Garvey bụ ọkà mmụta ama ama na onye nyocha jikọtara ya na ọtụtụ ụlọ ọrụ ama ama, gụnyere Mahadum Alabama na Birmingham, Mahadum Aston, na Birmingham Veterans Affairs Medical Center. Nzụlite agụmakwụkwọ ya na ahụmịhe ọkachamara gbasara ọtụtụ ọzụzụ n'ime ngalaba ahụike na sayensị. Dr. Garvey enyela nnukwu onyinye na ngalaba nke endocrinology na metabolism, nutrition and dietetics, biochemistry and molecular bayoloji, yana ọgwụ izugbe na nke ime, na-elekwasị anya na usoro obi na obi. Aghọtala ọrụ ya n'ọtụtụ ebe ma kwanyere ya ùgwù, nke akpọrọ aha ya onye nyocha nke ukwuu na ngalaba Cross-Field maka 2023 na 2024, na-egosipụta mmetụta dị ukwuu na mmetụta nke nyocha ya na mpaghara sayensị sara mbara.

Mmasị nyocha na nka Dr. Garvey gbatịrị akụkụ dị iche iche nke ọrịa metabolic na njikwa ha. O tinyela aka n'ịmụ banyere ọrịa shuga mellitus, oke ibu, na nsogbu ndị metụtara ya, na-achọ ikpughe usoro ọgwụgwọ ọhụrụ yana melite nsonaazụ onye ọrịa. Ọrụ ya gụnyere nchọpụta sayensị bụ isi, nnwale ụlọ ọgwụ, na ọmụmụ ntụgharị, na-ejikọta ọdịiche dị n'etiti nchọpụta ụlọ nyocha na ngwa ahụike ụwa n'ezie. Site na nyocha ya buru ibu, Dr. Garvey enyela aka na nghọta miri emi nke usoro ndị na-akpata ọrịa metabolic ma nyere aka ịkpụzi ụkpụrụ nduzi ụlọ ọgwụ na usoro ọgwụgwọ na ngalaba nke endocrinology na metabolism. Dọkịta William T. Garvey ka edepụtara na ntụnye aka nke ntụaka ^[4].

▎ Okwu ndị dị mkpa

[1] Nowak M, Nowak W, Grzeszczak W. Tirzepatid - abụọ GIP/GLP-1 agonist receptor - ọgwụ antidiabetic ọhụrụ nwere ike ịrụ ọrụ metabolic na ọgwụgwọ ụdị ọrịa shuga 2[J]. Endokrynologia Polska, 2022,73 (4): 745-755.DOI: 10.5603/EP.a2022.0029.

[2] Amaghị aha. Tirzepatid: A Dual Glucose-dabere na Insulinotropic Polypeptide na Glucagon-dị ka Peptide-1 Agonist maka njikwa nke ụdị 2 ọrịa shuga mellitus: Erratum.[J]. Akwụkwọ akụkọ American Therapeutics, 2023,30 (3): e311.DOI: 10.1097/MJT.000000000001634.

[3] Forzano I, Varzideh F, Avisato R, et al. Tirzepatid: Mmelite usoro[J]. Akwụkwọ akụkọ International nke Science Molecular, 2022,23 (23) .DOI: 10.3390/ijms232314631.

[4] Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatid otu ugboro kwa izu maka ọgwụgwọ oke ibu na ndị nwere ụdị ọrịa shuga 2 (SURMOUNT-2): onye kpuru ìsì abụọ, randomized, multicentre, placebo-controlled, phase 3 trial[J]. Lancet, 2023,402 (10402):613-626.DOI:10.1016/S0140-6736(23)01200-X.

[5] Fontanella RA, Ghosh P, Pesapane A, et al. Tirzepatid na-egbochi neurodegeneration site na ọtụtụ ụzọ molekụla[J]. Akwụkwọ akụkọ ọgwụ ntụgharị, 2024,22 (1).DOI:10.1186/s12967-024-04927-z.

[6] Ma Z, Jin K, Yue M, et al. Ọganihu nyocha na GIP/GLP-1 Onye na-anabata Coagonist Tirzepatid, Star Rising in Type 2 Diabetes[J]. Akwụkwọ akụkọ nyocha ọrịa shuga, 2023,2023.DOI:10.1155/2023/5891532.

Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.