Tirzepatid 45 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 njedebe nke ndị na-anabata GLP-1 dị na ọgwụgwọ ụdị 2 metabolism na oke ibu. Ọ bụ ezie na ndị na-anabata GLP-1 egosilarị arụmọrụ dị mma na njikwa glucose ọbara na mbelata ibu, ndị ọkà mmụta sayensị achọpụtala na ka ha na-arụ ọrụ GLP-1 receptor, mmetụta ha na-arụ ọrụ na onye na-anabata GIP adịghị ike, nke ruo n'ókè ụfọdụ na-egbochi mmetụta ọgwụgwọ ọgwụ. Ya mere, otu nyocha na mmepe na-agba mbọ imepụta ụdị ọgwụ ọhụrụ nke nwere ike ịgbalite ma GIPR na GLP-1R n'otu oge, na-atụ anya inweta njikwa glucose ọbara zuru oke ma dị irè na njikwa ibu ^[1]. .

N'oge usoro nyocha na mmepe nke Tirzepatid, ndị ọkà mmụta sayensị emeela ọtụtụ nyocha nyocha na nyocha ụlọ ọgwụ. Nke mbụ, n'ime usoro nyocha nke izizi, a na-enyocha njirimara ọgwụ ọgwụ nke Tirzepatid site na nnwale anụmanụ, na ikike ọ nwere na njikwa glucose ọbara na mbelata ibu. Nsonaazụ gosiri na Tirzepatid nwere ike belata ọkwa glucose ọbara n'ụdị anụmanụ ma rụọ ọrụ nke ọma na njikwa ibu. Nchọpụta ndị a dị mma tọrọ ntọala siri ike maka ule ụlọ ọgwụ na-esote.

Mgbe nke ahụ gasịrị, Tirzepatid batara n'ọkwa nnwale ụlọ ọgwụ, gụnyere ule I, II, na III. N'ime usoro ikpe nke mbụ, a na-enyocha nchekwa, nnabata, na pharmacokinetic nke ọgwụ ahụ, na nsonaazụ ya gosipụtara na Tirzepatid nwere ezigbo nchekwa na nnabata. Nnwale nke usoro nke abụọ nyochara ịdị irè na nchekwa nke ọgwụ Tirzepatid dị iche iche na ndị ọrịa nwere ụdị 2 metabolism, ma buru ụzọ kpebie oke dose ya dị mma. Ọnwụnwa ụlọ ọgwụ kachasị mkpa nke III, dị ka usoro ọmụmụ SURPASS, kpuchiri ọnụ ọgụgụ buru ibu nke ndị ọrịa nwere ụdị ọrịa shuga 2. Nsonaazụ gosiri na Tirzepatid dị elu karịa ndị agonists nnabata GLP-1 dị ugbu a, dị ka semaglutide, n'ibelata glucose na ibu ọbara. Nsonaazụ nsonaazụ a nyere nkwado nkwado siri ike maka ngwa ahịa nke Tirzepatid ^[1].

Tirzepatid bụ polypeptide nke mejupụtara amino acid 39, nke emezigharịrị n'ụdị amino asịd nke ọ bụla iji kwalite nkwụsi ike na ịdị irè ya. Nhazi nhazi a pụrụ iche na-enyere Tirzepatid aka ijikọ mmetụta nke homonụ incretin abụọ, GIP na GLP-1, n'ime otu molekul, ma mee ka ndị na-anabata homonụ na-etinye aka na njikwa glucose ọbara site na usoro ihe omume abụọ. Kpọmkwem, Tirzepatid nwere ike ime ma pancreas na sistemu ụjọ nke etiti. N'otu aka ahụ, ọ na-akwalite mmepụta insulin ma na-egbochi mwepụta glucagon, si otú a na-ebelata glucose ọbara n'ụzọ dị irè; N'aka nke ọzọ, site n'igbu oge nkwụsị nke gastric na ịba ụba satiety, ọ na-ebelata agụụ na iri nri, ma si otú a na-enweta njikwa ibu. Usoro ihe omume abụọ a na-enye Tirzepatid uru pụrụ iche na ọgwụgwọ ụdị 2 metabolism na oke ibu, na-enye ndị ọrịa nhọrọ ọgwụgwọ zuru oke ^..

Kedu ihe bụ usoro nke Tirzepatid?

Tirzepatid na-ebelata glucose ọbara site na ọtụtụ usoro na-arụkọ ọrụ ọnụ, dị ka ndị a: ịgbalite onye na-anabata GLP-1: Tirzepatid na-ejikọta ya na onye na-anabata GLP-1 na mkpụrụ ndụ β pancreatic, na-eṅomi mmetụta nke GLP-1 eke. GLP-1 bụ homonụ nke emepụtara na eriri afọ ma dị oke mkpa maka idowe glucose homeostasis 2. Ọ nwere ike ịkwalite njikọ insulin, mmepụta insulin, na mmetụta glucose, yana ibelata secretion glucagon iji kwalite satiety na igbochi agụụ 2.

Nrụ ọrụ a nwere ike ịkwalite mmepụta insulin. Insulin bụ isi homonụ na-ebelata glucose n'ọbara n'ime ahụ, nke nwere ike ịbawanye nnabata na ojiji nke glucose site na sel, si otú ahụ belata ọkwa glucose ọbara. N'ime ndị ọrịa nwere ụdị ọrịa metabolism nke 2, insulin ezughi oke ma ọ bụ sel sel na-ahụ maka insulin na-ebelata, na-eduga n'ịbawanye glucose ọbara. Tirzepatid na-abawanye mmepụta insulin site na ịgbalite onye na-anabata GLP-1, nke na-enyere aka melite njikwa glucose ọbara. N'otu oge ahụ, ịgbalite GLP-1 nnabata nwekwara ike igbochi ntọhapụ nke glucagon. Glucagon na-akwalitekarị glycogenolysis na gluconeogenesis na steeti ibu ọnụ, na-abawanye mmepụta glucose ọbara. Site na igbochi mmetụta glucagon, Tirzepatid na-ebelata isi iyi nke glucose ọbara, nke na-enyere aka ịchịkwa glucose ọbara ^[2] (Anonymous, 2023).

Ịkwalite onye na-anabata GIP: Tirzepatid na-arụ ọrụ na onye na-anabata GIP n'otu oge. Mgbe arụ ọrụ ya gasịrị, ọ nwere ike ịkwalite mmetụta insulin na nzuzo. Onye na-anabata GIP na-anọkarị na anụ ahụ dịka mkpụrụ ndụ beta pancreatic. Mgbe ịgbalitechara ya, site na njikwa nke ụzọ mgbaàmà intracellular, secretion insulin na-abawanye, na nzaghachi nke mkpụrụ ndụ na insulin na-eme ka ọ dịkwuo mma, si otú a na-ebelata glucose ọbara n'ụzọ dị irè karị 2. Tirzepatid bụ nke mbụ na klas dual glucagon-dị ka peptide-1 na glucose na-adabere na glucose na-adabere n'ụdị insulinotropic polypeptide (GIP) nke analogues nke okenye na-akwado maka ọgwụgwọ nke ụdị insulinotropic polypeptide (GIP). mmega ahụ 2. Tirzepatid bụ usoro kemịkalụ sịntetik dabere na usoro GIP, nke nwere peptide 39-amino acid mejupụtara. Ọ na-abawanye mmepụta insulin, na-ebelata ntọhapụ nke glucagon n'ụzọ dabere na glucose, na-ebelata ọnụ ọgụgụ glucose ọbara na-ebu ọnụ na postprandial, na-akwalite satiety, na-ebelata ibu, na-egbu oge ịpụpụ afọ.

Mmetụta agonist abụọ na-anabata ihe na-eme Tirzepatid dị irè karị n'ịkwalite mmepụta insulin na igbochi ntọhapụ glucagon karịa otu GLP-1 agonists ^[2]..

Na-egbu oge mkpofu gastric na ịba ụba satiety: Tirzepatid nwere ike igbu oge ịwụfu afọ, gbatịa oge obibi nri n'ime afọ, na-ebelata nnabata nke nri na-edozi ahụ, wee zere mmụba dị ukwuu na glucose ọbara postprandial. N'ihe ọmụmụ izizi 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 nke ịsachapụ 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 nwere ma na-enweghị ụdị 2 metabolism metabolism, Tirzepatid otu ugboro kwa izu (≥5 na ≥4.5mg, n'otu n'otu) na-egbu oge ịpụpụ gastric mgbe otu ọgwụ gasịrị. N'ime ndị sonyere nwere ahụike, a na-ebelata mmetụta a mgbe ọtụtụ doses nke Tirzepatid ma ọ bụ dulaglutide ^{[3] gasịrị.} .

N'otu oge ahụ, ọ pụkwara ime ihe na usoro nhụjuanya nke etiti, na-abawanye satiety, na ibelata agụụ na nri oriri. Site n'ịchịkwa oriri, ọ na-enyere aka ịchịkwa ọkwa glucose ọbara n'ụzọ na-apụtaghị ìhè, karịsịa maka nsogbu oke ibu nke ndị ọrịa nwere ụdị 2 metabolism na-esonyere ya, ma na-enyere aka melite nguzogide insulin na ọnọdụ metabolic zuru oke ^[2]..

Imeziwanye mmetụta insulin na metabolism lipid: Achọpụtala Tirzepatid na-abawanye ọkwa adiponectin, nke bụ adipocytokine metụtara mmetụta insulin. Mmụba nke adiponectin na-enyere aka imeziwanye mmetụta insulin, na-eme ka mkpụrụ ndụ na-enwe mmetụta nke insulin, wee si otú a na-ewelite ma jiri glucose mee ihe nke ọma, na-ebelata glucose ọbara ^[2]..

Na mgbakwunye, Tirzepatid nwekwara ike imeziwanye profaịlụ lipid ma nwee mmetụta nchebe na ahụike obi. Achọpụtara Tirzepatid na ọ nwere ike ịkwalite ọbara mgbali elu, belata obere njupụta lipoprotein (LDL) cholesterol na triglycerides ^[4] .Nke a na-akwado uru ya zuru oke na njikwa glucose ọbara.

Nnyocha metụtara ya

Ịdị irè na njikwa ibu na ndị ọrịa nwere oke ibu na ụdị 2 metabolism: 

Ọtụtụ ọmụmụ ụlọ ọgwụ ekwenyela na mmetụta mbelata ibu dị ukwuu: N'ime nyocha nke aha ya bụ 'SURMOUNT-2', nnwale a bụ nkeji 3, kpuru ìsì abụọ, nke enweghị usoro, nnwale 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 hemoglobin glycated (HbA₁c) nke 7-10% na-enyeghị usoro ka ọ nata ọgwụ Tirzepatid subcutaneous otu ugboro kwa izu (10mg ma ọ bụ 15mg) ma ọ bụ placebo maka izu 72. Nsonaazụ gosiri na n'izu 72, pasent nke ọnwụ dị na Tirzepatid 10mg na 15mg dị iche iche bụ -12.8% na -14.7%, n'otu n'otu, ebe na placebo otu bụ -3.2%. Atụmatụ ọgwụgwọ dị iche iche nke Tirzepatid 10mg na 15mg ma e jiri ya tụnyere placebo bụ -9.6 pasent na -11.6 pasent, n'otu n'otu, ha abụọ bụ ọnụ ọgụgụ dị ịrịba ama (p | 0.0001). Na mgbakwunye, ọtụtụ ndị ọrịa na-agwọ Tirzepatid ruru n'ókè nke mfu nke 5% ma ọ bụ karịa (79 - 83% vs 32%) ^[5] (Garvey WT, 2023). 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, kamakwa ọ rụrụ ọrụ dị mma na njikwa glucose ọbara ^..

Mmetụta dị mma na neuropathy metụtara metabolism: 

Ụfọdụ ọmụmụ egosila na glucagon-dị ka peptide 1 agonists (GLP1-RAs) nwere ike ibelata ihe ize ndụ nke ịda mbà n'obi na ndị ọrịa nwere ụdị 2 metabolism site na imeziwanye ebe nchekwa, mmụta, na imeri adịghị ike nghọta. Dị ka onye na-anabata insulin polypeptide receptor agonist abụọ (GIP-RA) / GLP-1RA, Tirzepatid mụrụ maka mmetụta ya na nrịbama nke uto neuronal (CREB na BDNF), apoptosis (BAX / Bcl2 ratio), ọdịiche (pAkt, MAP2, GAP43, na AGBL4), na insulin resistance (GLUT, 1) na insulin resistance (GLUT4) Neuroblastoma cell line (SHSY5Y). Nsonaazụ maka oge mbụ kwusiri ike na ọrụ Tirzepatid na-arụ ọrụ n'ịgbalite ụzọ pAkt/CREB/BDNF na mgbago mgbago mgbago ala, yana ịdị irè ya na neuroprotection. 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 wee merie nguzogide insulin nke neuronal, na-enye nghọta ọhụrụ maka mmelite nke neuropathy metụtara metabolism ^[6]. .

Ọganihu nyocha na ọgwụgwọ ụdị 2 metabolism: 

Ụfọdụ ọmụmụ egosila na Tirzepatid, dị ka ụdị ọgwụ hypoglycemic ọhụrụ, aghọwo onye mbụ GIP/GLP-1R agonist kwadoro maka ọgwụgwọ nke metabolism na United States. Ekwuputala ya na ọ nwere mmetụta dị ịrịba ama na mbelata glucose-ọbara na mbelata ibu n'ọtụtụ nnukwu nnwale ụlọ ọgwụ, yana ihe akaebe na-egosi na ọ nwekwara ikike dị ukwuu na nchekwa 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 n'ọhịa nke ọrịa imeju na-adịghị egbu egbu (NAFLD), renal na neuroprotection, wdg ^[7]..

Mmetụta ogologo oge nke T irzepatide na ahụike obi: 

Tirzepatid nwere ike ibelata ihe ize ndụ nke ọrịa obi site n'ịkwalite ibu ibu. Nnyocha ahụ nyochara mmetụta Tirzepatid na oke ibu na ọrịa obi na ọrịa obi na ndị okenye America ^[8] . Nnyocha ahụ chọpụtara na n'etiti ndị okenye America tozuru oke maka ọgwụgwọ Tirzepatid, mgbe ọgwụgwọ ya na 15mg nke Tirzepatid gasịrị, a na-eme atụmatụ na 70.6% na 56.7% nke ndị okenye nwere mbelata nke ≥15% na ndị mmadụ ≥15%, nke pụtara na ọnụ ọgụgụ ndị mmadụ ruru ≥20. 58.8% N'ime ndị mmadụ na-enweghị ọrịa obi, ihe ize ndụ nke afọ 10 nke ọrịa obi 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 2 nde ọrịa ọrịa obi nwere ike igbochi n'ime afọ 10.

Na mmechi, Tirzepatid bụ agonist dual agonist nke GIP na GLP-1 ndị na-anabata ya ma dị oke mkpa na ọgwụgwọ ụdị 2 metabolism na oke ibu. Ọ nwere ike na-akwalite mmepụta insulin nke ọma, na-egbochi secretion glucagon, na-ahazi glucose ọbara nke ọma, belata ihe ize ndụ nke nsogbu, melite ọrụ nke mkpụrụ ndụ beta pancreatic, na-egbu oge na-aga n'ihu nke metabolism. 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, ọ na-egosi ike na ọgwụgwọ nke ọrịa ndị metụtara metabolic abnormality dị ka steatohepatitis na-adịghị egbu egbu, ọrịa apnea na-ehi ụra, na nkụda obi, ma nwee ike imeziwanye ọtụtụ ihe ngosi metabolic n'otu oge, na-enye atụmatụ ọgwụgwọ zuru oke. Usoro nchịkwa injection ya kwa izu dị mma maka iji yana nwee ike melite nnabata ọgwụgwọ ndị ọrịa. Site n'ịchịkwa glucose na ịdị arọ nke ọbara n'ụzọ dị irè na ibelata ihe ize ndụ nke nsogbu, ọnọdụ anụ ahụ nke ndị ọrịa nwere ike ime ka ọ dịkwuo mma, ikike ime ihe kwa ụbọchị na ndụ ndụ ha nwere ike ịbawanyewanye, ntụkwasị obi ha na njikwa ọrịa nwere ike ịbawanye elu, a ga-ebelata ibu nke uche ha, na ime mgbanwe mmekọrịta ha nwere ike ime ka ọ dịkwuo mma.

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 metabolism metabolism, oke ibu, na nsogbu ndị metụtara ya, na-achọ ikpughe usoro ọgwụgwọ ọhụụ 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 ^[5].

▎ Okwu ndị dị mkpa

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

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

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[5] Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatid otu ugboro kwa izu maka ọgwụgwọ oke ibu na ndị nwere ụdị 2 metabolism (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.

[6] 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.

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[8] Wong ND, Karthikeyan H, Fan W. ntozu ndị mmadụ na US na atụle mmetụta ọgwụgwọ Tirzepatid na oke oke ibu na ihe omume ọrịa obi [J]. Ọgwụ na ọgwụgwọ obi obi, 2024.DOI:10.1007/s10557-024-07583-z.

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