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▎ Ọdịdị Tirzepatide
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 Arọ molekụla: 4813 g/mol Nọmba CAS: 2023788-19-2 PubChem CID: 163285897 Ụdị okwu: Zepbound; Mounjaro |
▎ Nyocha Tirzepatide
Kedu ihe ndabere nyocha nke Tirzepatide?
Tirzepatide bụ ọgwụ polypeptide sịntetik. Mmepe ya sitere na nghọta miri emi nke oke nke ndị na-anabata GLP-1 dị na ọgwụgwọ ụdị 2 metabolism mellitus (T2DM) na oke ibu. Ọ bụ ezie na GLP-1 agonists anabatara egosila ọmarịcha 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 Tirzepatide nke ọma site na nnwale anụmanụ, na-enyocha ikike ya na njikwa glucose ọbara na mbelata ibu. Nsonaazụ gosiri na ọ nwere ike ibelata ọkwa glucose ọbara n'ụzọ dị ukwuu na 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. Ọnwụnwa nke usoro nke mbụ tụlere nchekwa, nnabata, na akụrụngwa ọgwụ ọgwụ. Nsonaazụ gosiri na Tirzepatide nwere ezigbo nchekwa na nnabata. Ọnwụnwa nke Abụọ nyochara arụmọrụ na nchekwa dị iche iche nke Tirzepatide 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 Tirzepatide dị elu karịa ndị na-anabata GLP-1 dị ugbu a, dị ka semaglutide, na-ebelata glucose ọbara na ịdị arọ, na-enye ihe akaebe siri ike maka ngwa ahịa Tirzepatide [1]..
Kedu ihe bụ usoro nke Tirzepatide?
Tirzepatide na-ebelata glucose ọbara site na ọtụtụ usoro na-arụkọ ọrụ ọnụ. Mgbe ị na-arụ ọrụ onye na-anabata GLP-1, Tirzepatide 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 a na-emepụta 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 n'ime 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'ọkwa glucose ọbara. Site na ịgbalite onye na-anabata GLP-1, Tirzepatide 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, Tirzepatide na-ebelata isi iyi nke glucose ọbara, na-enye aka na njikwa glucose ọbara [2]..
Mgbe ị na-arụ ọrụ onye na-anabata GIP, Tirzepatide 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 β-pancreatic. Mgbe arụ ọrụ ya gasịrị, site na nnyefe nke ụzọ mgbaàmà intracellular, mmepụta insulin na-abawanye, yana nnabata cell na-anabata insulin na-abawanye, si otú a na-ebelata ọkwa glucose ọbara nke ọma.
Tirzepatide bụ nke mbụ na klas nke abụọ glucagon-dị ka peptide-1 na glucose-based insulinotropic polypeptide (GIP) analog, nke akwadoro maka ọgwụgwọ nke ndị okenye nwere T2DM dị ka ihe mgbakwunye nri na mmega ahụ. Tirzepatide 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 Tirzepatide dị irè karịa otu GLP-1 agonists na-anabata ya n'ịkwalite mmepụta insulin na igbochi ntọhapụ glucagon [2]..
Tirzepatide nwekwara ike igbu oge mkpofu afọ na ịbawanye satiety. Ọ nwere ike na-egbu oge ịwụfu afọ, na-agbatị oge obibi 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 Tirzepatide na mkpofu gastric dị ka nke GLP-1 agonists na-anabata ya. N'ime oke oke oke nri kpatara nri, ogo igbu oge igbu oge nke Tirzepatide dị ka 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, Tirzepatide otu ugboro kwa izu (≥5 mg na ≥4.5 mg, n'otu n'otu) na-egbu oge mkpofu afọ mgbe otu ọgwụ gasịrị. N'ime ndị sonyere nwere ahụike, a na-ebelata mmetụta ahụ mgbe ọtụtụ doses nke Tirzepatide ma ọ bụ dulaglutide (Urva S, 2020) gasịrị. N'otu oge ahụ, ọ nwekwara ike ime ihe na usoro nhụjuanya nke 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 Tirzepatide 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, Tirzepatide nwekwara ike melite profaịlụ lipid ma nwee mmetụta nchebe na ahụike obi. E gosipụtara Tirzepatide na-enwe ike imeziwanye ọbara mgbali elu, belata obere lipoprotein (LDL) cholesterol na triglycerides [3] , na-akwadokwa uru ya zuru oke na njikwa glucose ọbara.
Isi mmalite: PubMed [5]
Nnyocha metụtara ya
Ịdị irè na njikwa ibu na ndị ọrịa nwere oke ibu na ụdị 2 metabolism
Ọtụtụ ọmụmụ ụlọ ọgwụ ekwenyela na uru Tirzepatide 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, 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 Tirzepatide otu ugboro kwa izu (10 mg ma ọ bụ 15 mg) ma ọ bụ placebo maka izu 72.
Nsonaazụ gosiri na n'izu 72, pasent nke ọnwụ dị na Tirzepatide 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 Tirzepatide 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 Tirzepatide 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, Tirzepatide abụghị naanị ibelata ibu ahụ mana ọ nwekwara mmetụta dị mma na njikwa glucose ọbara ..
Mmetụta dị mma na neuropathy metụtara metabolism
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, Tirzepatide 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 ọrụ Tirzepatide n'ịgbalite ụzọ pAkt / CREB / BDNF na mgbago mgbago mgbago ala, yana arụmọrụ neuroprotective ya. O gosikwara na Tirzepatide nwere ike igbochi mmetụta ndị metụtara hyperglycemia na nguzogide insulin na ọkwa neuronal. Ya mere, Tirzepatide nwere ike imeziwanye neurodegeneration nke hyperglycemia kpatara ma merie nguzogide insulin neuronal, na-enye nghọta ọhụrụ maka mmelite nke neuropathy metụtara metabolism [5]..
Ọganihu nyocha na ọgwụgwọ ụdị 2 metabolism
Ụfọdụ ọmụmụ egosila na dịka ụdị ọgwụ hypoglycemic ọhụrụ, Tirzepatide abụrụla agonist GIP/GLP-1R nke mbụ kwadoro maka ọgwụgwọ metabolism na United States. Ekwenyere na ọ nwere mmetụta dị ukwuu n'ibelata glucose ọbara na ibelata ibu ahụ n'ọtụtụ nnukwu ule ụlọ ọgwụ, na e nwere ihe àmà na-egosi na ọ nwekwara ikike dị ukwuu na nchebe obi.
Na mgbakwunye, echiche nke peptides sịntetik emeghela ọtụtụ ohere amaghi ama maka Tirzepatide. 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
Tirzepatide nwere ike ibelata ihe ize ndụ nke ọrịa obi site n'ịkwalite ibu ibu. Otu nnyocha nyochara mmetụta Tirzepatide 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 Tirzepatide, mgbe ọgwụgwọ na 15 mg nke Tirzepatide 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.
N'ikpeazụ, Tirzepatide bụ agonist dual agonist nke GIP na GLP-1 ndị na-anabata ya, nke dị oke mkpa na ọgwụgwọ T2DM na oke ibu. Ọ nwere ike na-akwalite 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 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, o gosila ikike n'ịgwọ ọrịa ndị metụtara ọrịa metabolic dị ka steatohepatitis na-adịghị egbu egbu, ọrịa apnea ụra, na nkụda mmụọ. Ọ nwere ike melite otutu 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 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 [4].
