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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.
Nchịkọta nke Triple Agonists
N'ime afọ ndị na-adịbeghị anya, site n'ịbawanye nyocha n'ime pathogenesis nke ọrịa metabolic, mmepe nke ọgwụ agonist multi-target na-elekwasị anya na ọtụtụ ndị na-anabata hormone aghọwo isiokwu na-ekpo ọkụ. Retatrutid bụ agonist atọ dị ọhụrụ nke insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), na ndị na-anabata glucagon (GC).
(1) Ndabere gbasara anụ ahụ nke ọrụ nnabata homonụ
Onye na-anabata GIP: GIP bụ hormone na-ezobe insulin n'ime eriri afọ nke mkpụrụ ndụ K na-ezobere na eriri afọ, na-ewepụta ngwa ngwa mgbe nri gasịrị. Mgbe ejikọtara ya na onye na-anabata GIP, GIP na-akpali mmepụta insulin, yana mmetụta a na-akpali akpali bụ glucose dabere, nke pụtara na ka ọkwa glucose ọbara na-ebili, GIP na-eme ka mmetụta insulin na-ezobe ya, na-enyere aka ịnọgide na-enwe ọkwa glucose ọbara kwụsiri ike. Na mgbakwunye, GIP na-ekere òkè na nhazi nke metabolism lipid, na-emetụta ọdịiche adipocyte na mkpokọta lipid.
Fig. 1. Ọgwụ RETA ma ọ bụ SEMA na-ebelata ibu ahụ ma na-eme ka glucose ọbara na-ebu ọnụ. b, Epididymal ọcha adipose anụ ahụ dị arọ ka agbakọrọ na njedebe. c A na-agbakọ ọnụ ọgụgụ glucose ọbara na-ebu ọnụ na mmalite yana n'oge ọmụmụ ihe niile n'oge egosipụtara ruo mgbe njedebe. d Tumor engraftment ma ọ bụ ' tumor take ' na-akọ.
Onye na-anabata GLP-1: GLP-1 bụ nke sel intestinal L na-ezobe ya ma nwee mmetụta insulinotropic na-adabere na glucose, na-eme ka njikọ insulin na ntọhapụ, na-egbochi secretion glucagon, na ibelata mmepụta glucose imeju. GLP-1 na-egbu oge mkpofu afọ, na-abawanye satiety, ma si otú a na-ebelata oriri. Ọ nwere mmetụta nchebe na ịba ụba na mkpụrụ ndụ beta nke pancreatic, na-enyere aka ịnọgide na-arụ ọrụ pancreatic.
3. GC Nnabata:
Mgbe ejikọtara ya na onye na-anabata GC, glucagon na-arụ ọrụ na imeju site na ịkwalite glycogenolysis na gluconeogenesis, si otú a na-ebuli ọkwa glucose ọbara. Na lipid metabolism, ọ na-akwalite lipolysis, na-abawanye ntọhapụ na oxidation nke ọdụdụ asịd maka ume. N'okpuru ọnọdụ physiological nkịtị, a na-egbochi secretion glucagon mgbe ọkwa glucose ọbara na-ebili iji nọgide na-enwe nguzozi nke glucose.
(2) Uru nke Omume Agonist Atọ
Dị ka agonist ugboro atọ, Retatrutid nwere ike mee ka ndị nnata atọ a rụọ ọrụ n'otu oge, na-enwe mmetụta synergistic. Site na ịgbalite ndị na-anabata GIP na GLP-1, ọ na-eme ka insulin na-adabere na glucose, na-ebelata ọkwa glucose ọbara nke ọma. Mmụba satiety na mkpofu afọ na-egbu oge nke nnabata GLP-1 na-ebute, yana lipolysis nke nkwalite nnabata GC kwalitere, na-enye aka na njikwa ibu. Usoro a nke ezubere iche maka ime ihe na-enye usoro nhazi nke usoro pathophysiological dị iche iche metụtara ọrịa metabolic.
Usoro nke Omume Retatrutid na Ọrịa Metabolic
Ọrịa metabolic bụ otu ọnọdụ nke mmebi nke usoro metabolic na-ebute n'ime ahụ, gụnyere ọnọdụ nkịtị dị ka ọrịa shuga, oke ibu, na ọrịa imeju na-adịghị egbu egbu. Retatrutid na-arụ ọrụ ya na ọrịa metabolic ndị a site na njirimara agonist ya pụrụ iche.
(1) Usoro eji eme ihe na ọrịa shuga
Regulation Glucose: Retatrutid na-arụ ọrụ GIP na GLP-1 ndị na-anabata ya, na-eme ka insulin na-adabere na glucose. Mgbe ọkwa glucose dị n'ọbara na-ebili, ọ na-eme ka mkpụrụ ndụ beta nke pancreatic na-emepụta insulin, na-akwalite nnabata glucose na itinye n'ọrụ, si otú a na-ebelata ọkwa glucose ọbara. Site na igbochi secretion glucagon na ibelata mmepụta glucose imeju, ọ na-eme ka ọkwa glucose dị n'ọbara kwụsie ike. N'ime ule ụlọ ọgwụ metụtara ndị ọrịa nwere ụdị ọrịa shuga 2, ọgwụgwọ Retatrutid butere mbelata dị ukwuu na ma ibu ọnụ na ọkwa glucose ọbara mgbe nri gasịrị.
Nchedo mkpụrụ ndụ beta nke pancreatic: ịgbalite GLP-1 nnabata ọ bụghị naanị na-akwalite mmepụta insulin kamakwa ọ na-enwe mmetụta nchebe na mmụba na mkpụrụ ndụ beta nke pancreatic. Retatrutid nwere ike nweta nke a site n'ịgbalite GLP-1 onye na-anabata ya, na-ebelata beta cell apoptosis, na-abawanye ọnụọgụ na ọrụ ha, si otú a na-eme ka ikike nzuzo insulin dịkwuo elu na ịnọgide na-enwe ọkwa glucose ọbara kwụsiri ike ruo ogologo oge.
(2) Usoro nke ime ihe na oke ibu
Iwu nke oriri ume: Retatrutid na-eme ka ndị na-anabata GLP-1 rụọ ọrụ, na-egbu oge ịwụfu afọ, na-agbatị oge nri n'ime afọ, na-abawanye satiety, na ibelata oriri. Ọ nwere ike na-eme ihe na usoro nhụjuanya nke etiti iji mezie neurotransmitters metụtara agụụ, dị ka igbochi ntọhapụ nke orexin, na-ebelata agụụ, ma si otú ahụ na-achịkwa oriri ike.
Mmefu ike na-abawanye: ịgbalite onye nnabata GC na-akwalite lipolysis, na-abawanye ntọhapụ na oxidation nke fatty acids maka mmepụta ike. Ọxidation nke fatty acids na-enye ahụ ike, na-ebelata nchekwa abụba, ma na-enyere aka n'ibelata ibu. Ịgbalite onye na-anabata GIP na-ekerekwa òkè na nhazi metabolism ume, na-abawanye mmefu ike.
Ọgụgụ 2 ọgwụgwọ RETA na-ebelata ibu ahụ na adiposity, na-eme ka glucose ọbara na-ebu ọnụ. A na-akọ mgbanwe pasentị n'ịdị arọ ahụ site na ntọala. b Epididymal na-acha ọcha adipose anụ ahụ na-atụ n'ebe njedebe wee mee ka ọ dị nhata n'ịdị arọ ahụ. c A na-agbakọ ọnụ ọgụgụ glucose ọbara na-ebu ọnụ na mmalite yana n'oge ọmụmụ ihe niile n'oge egosipụtara ruo mgbe njedebe.
(3) Usoro eji eme ihe na ọrịa imeju na-adịghị egbu egbu
Melite metabolism lipid imeju: Retatrutid na-eme ka onye na-anabata GC rụọ ọrụ, na-akwalite mmebi na β-oxidation nke abụba na imeju, si otú a na-ebelata mkpokọta abụba na imeju. Ịgbalite ndị na-anabata GIP na GLP-1 nwere ike ịhazi okwu nke mkpụrụ ndụ ihe nketa metụtara metabolism lipid na imeju, na-achịkwa okwu nke ndị na-ebugharị fatty acid na fatty acid oxidases, si otú ahụ na-akwalite nnabata abụba na oxidation, ma na-emewanyewanye metabolism lipid hepatic.
Mmetụta insulin na-emewanyewanye: ka ọ na-eme ka nchịkwa glucose na-abawanye ma na-abawanye mmepụta insulin, Retatrutid nwere ike ịkwalite mmetụta insulin imeju site na ịgbalite ndị na-anabata GLP-1. Mmetụta insulin na-abawanye na-eme ka nzaghachi imeju na-anabata insulin, na-egbochi mmepụta glucose imeju nke ọma, na-ebelata njikọ nke de novo fatty acid, wee si otú a belata steatosis imeju.
Ngwa na Mmetụta Retatrutid na Ọrịa Metabolic
(1) Ngwa na ọrịa shuga
Mmetụta nchịkwa lycemic: Retatrutid na-egosiputa mmetụta nchịkwa glycemic dị ukwuu na ndị ọrịa nwere ụdị ọrịa shuga 2. Dị ka data si kwuo, ndị ọrịa a na-emeso ya na Retatrutid gosipụtara mbelata dị ukwuu na haemoglobin A1c (HbA1c). N'ime nnwale a na-achịkwaghị achịkwa nke metụtara ndị ọrịa 353 nwere ụdị ọrịa shuga 2, ọkwa HbA1c na otu ọgwụgwọ Retatrutid belatara site na 1.64% site na ntọala, ebe enweghị mgbanwe dị ukwuu na otu placebo.
Tụnyere ọgwụ ndị ọzọ: Tụnyere ọgwụ antidiabetic ọdịnala dị ka metformin ma ọ bụ GLP-1 agonists na-anabata ya, Retatrutid na-egosipụta mmetụta njikwa glucose ọbara dị elu.
(2) Ngwa na oke ibu
Mmetụta mbelata ibu: Retatrutid na-egosipụta nrụpụta dị ukwuu na ọgwụgwọ oke ibu. N'ime ule ụlọ ọgwụ ezubere iche maka ndị ọrịa toro eto buru oke ibu, a hụrụ mbelata oke ibu mgbe izu iri anọ na asatọ ejiri ọgwụgwọ dị iche iche nke Retatrutid. N'otu ule, ndị ọrịa na-eji ọgwụ 12mg nke Retatrutid mee ihe na-enweta nkezi ịdị arọ nke 24.2% mgbe izu 48 gasịrị, ma e jiri ya tụnyere naanị 2.1% na otu placebo. Na mgbakwunye, 83% nke ndị sonyere na otu oke dose ahụ nwetara mfu nke 15% ma ọ bụ karịa, karịa nke 2% na otu placebo.
Mmetụta ogologo oge: Retatrutid na-ejigide mmetụta ọnwụ dị arọ nke ọma n'ime oge ọgwụgwọ. Nke a na-egosi na iji ogologo oge eme ihe nwere ike inye aka ịnọgide na-adị arọ ma gbochie ibughachi ibu, nke bara uru maka nlekọta ogologo oge nke oke ibu.
(3) Ngwa na ọrịa imeju abụba na-abụghị mmanya
Mbelata abụba imeju: N'ime ndị ọrịa nwere ọrịa imeju na-arịa ọrịa metabolic na-ejikọta ya na abụba abụba ≥10%, ọgwụgwọ Retatrutid butere mbelata nke ukwuu na abụba imeju. N'ime ule a na-achịkwaghị achịkwa, kpuru ìsì abụọ, ebe a na-achịkwa placebo, na izu 24, ọdịnaya abụba imeju belatara site na 81.4% na 82.4% site na ntọala na 8 mg na 12 mg otu dose, n'otu n'otu, ebe placebo otu mụbara site na 0.3%.
Uru na ike nke Agonist Triple
Retatrutid na-ahazi ọtụtụ ụzọ pathophysiological nke ọrịa metabolic site n'ịgbalite GIP, GLP-1 na ndị na-anabata GC n'otu oge. Site na njikwa glucose ọbara, njikwa ibu, na-emeziwanye metabolism lipid imeju, usoro a na-eme atụmatụ ọtụtụ ihe na-enye mgbazi zuru oke nke ọrịa metabolic ma e jiri ya tụnyere ọgwụ ndị ezubere iche, na-egosipụta ikike ilebara etiology dị mgbagwoju anya nke ọrịa metabolic. Data nnwale ụlọ ọgwụ dị adị na-egosi na Retatrutid enwetala mmetụta dị ukwuu na ọgwụgwọ ọrịa metabolic dị ka ọrịa shuga, oke ibu, na ọrịa imeju na-adịghị egbu egbu.
Mmechi
Dị ka agonist ugboro atọ, Retatrutid na-ekwe nkwa maka ọgwụgwọ ọrịa metabolic.
Isi mmalite
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[2] Kaur M, Misra S. Nyochaa nyocha retatrutide ọgwụ nyocha, onye nnọchi anya agonist atọ nke akwụkwọ akụkọ maka ọgwụgwọ oke ibu [J]. Akwụkwọ akụkọ European nke Clinical Pharmacology, 2024,80 (5): 669-676.DOI: 10.1007 / s00228-024-03646-0.
[3] Lopez DC, Pajimna JT, Milan MD, et al. 7792 arụmọrụ nke Retatrutid maka Mbelata ibu na Mmetụta Cardiometabolic ya n'etiti ndị okenye: Nyochaa usoro na Meta-Analysis[J]. Akwụkwọ akụkọ nke Endocrine Society, 2024,8 (Mgbakwunye_1): bvae163-bvae749.DOI:10.1210/jendso/bvae163.749.
[4] Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutid maka oke ibu - Ọnwụnwa nke 2 [J]. Akwụkwọ akụkọ ọgwụ New England, 2023,389 (6): 514-526.DOI: 10.1056/NEJMoa2301972.
[5] Doggrell SA Ọ bụ retatrutide (LY3437943), GLP-1, GIP, na glucagon agonist receptor glucagon bụ nzọụkwụ na-aga n'ihu na ọgwụgwọ ọrịa shuga na oke ibu?[J]. Echiche ndị ọkachamara na ọgwụ nyocha, 2023,32 (5): 355-359.DOI: 10.1080/13543784.2023.2206560.
Ngwaahịa dị maka naanị nyocha:
