By Cocer Peptides 
Ọnwa abụọ gara aga
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.
Ka ọrịa metabolic dị ka oke ibu, oke ibu, na ọrịa shuga na-aga n'ihu na-arị elu n'ụwa niile, ịchọ ọgwụ ọgwụgwọ dị irè aghọọla isiokwu na-ekpo ọkụ na ngalaba ahụike. Mazdutide, dị ka onye agonist dual receptor agonist, nwere ike rụọ ọrụ n'otu oge GLP-1 nnabata na onye na-anabata glucagon, a na-atụkwa anya na ọ ga-arụ ọrụ pụrụ iche na mbelata ibu na njikwa shuga ọbara, na-enye ohere ọhụrụ maka ọgwụgwọ ọrịa metabolic.
Ọgụgụ 1 Ọdịdị kemịkalụ nke Mazdutide.
Nkọwa nke Mazdutide
Mazdutide bụ GLP-1/glucagon dual receptor agonist, ọgwụ ọhụrụ maka ọgwụgwọ ọrịa metabolic. N'ime iri afọ ole na ole gara aga, mmepe ọgwụ ezubere iche maka ọrịa metabolic ka na-aga n'ihu. Ndị na-anabata GLP-1 na glucagon agonists egosipụtawo ụfọdụ mmetụta ọgwụgwọ mgbe ejiri ya naanị ya, mana ha nwekwara oke nke ha. Iji chọọ nhọrọ ọgwụgwọ kachasị mma, ndị nchọpụta lekwasịrị anya n'ịzụlite ọgwụ ndị nwere ike ime n'ọtụtụ ebumnuche n'otu oge, na-eduga n'ichepụta Mazdutide. Usoro mmepe ya enweela ọmụmụ ihe n'ụzọ siri ike na ule ụlọ ọgwụ dị iche iche, jiri nwayọọ nwayọọ na-akwado nchekwa na ịdị irè ya.
Usoro nke Omume
(1) Ntinye nke GLP-1 Nnabata
Iwu nke glucose homeostasis: GLP-1 bụ homonụ peptide nke sel intestinal L zoro ezo. Mgbe ịgbalite GLP-1 nnabata, Mazdutide na-ahazi glucose ọbara site n'ọtụtụ ụzọ. Ọ na-akwalite mmepụta insulin site na mkpụrụ ndụ beta pancreatic, na-eme ka mmetụta insulin dịkwuo elu, si otú a na-eme ka nnabata glucose na-arụ ọrụ ngwa ngwa, na-ebelata ọkwa glucose ọbara. Ọ na-egbochi secretion glucagon site na mkpụrụ ndụ α nke pancreatic ma na-ebelata mmepụta glucose imeju, na-eme ka ọ kwụsie ike n'ọbara.
Na-egbu oge mkpofu gastric: Mazdutide na-eme ka GLP-1 na-anabata ya, na-arụ ọrụ na sistemụ eriri afọ iji mee ka mkpofu gastric kwụsịlata. Nke a na-eme ka njide nri dị ogologo n'ime afọ, na-abawanye satiety na ibelata iri nri, si otú ahụ na-enyere aka ịchịkwa ibu.
Usoro nke agụụ: Mgbe GLP-1 na-arụ ọrụ nnabata, a na-ebunye akara na sistemu ụjọ nke etiti, na-arụ ọrụ na ebe nri hypothalamic iji mezie nzuzo nke neuropeptides metụtara agụụ, dị ka ibelata okwu neuropeptide Y (NPY) na ịba ụba proopiomelanocortin (POMC) na-ebelata nkwupụta, si otú ahụ na-akpali akpali echiche nke nri.
(2) Ịgbalite ndị na-anabata glucagon
Ịkwalite mmefu ike: Mgbe onye na-anabata glucagon na-arụ ọrụ site na Mazdutide, ọ na-akwalite mmebi abụba na fatty acid oxidation, na-amụba mmefu ike. Na mgbakwunye, ọ na-akwalite nkwupụta nke protein 1 (UCP1) na-enweghị njikọ, na-akwalite thermogenesis na anụ ahụ adipose agba aja aja, na-eme ka ahụ nwee ike metabolism na inye aka n'ibelata ibu.
Nhazi nke glucose metabolism: ịgbalite ndị na-anabata glucagon na-akwalite imeju glycogenolysis na gluconeogenesis. Agbanyeghị, n'okpuru mmetụta Mazdutide, mmetụta nkwado a abụghị naanị na-ebuli ọkwa glucose ọbara, kama ọ na-enweta usoro glucose ọbara nke ọma site na mmekọrịta mmekọrịta yana mmetụta nnabata GLP-1. Mgbe ọkwa glucose dị n'ọbara dị elu, mmetụta hypoglycemic nke nnabata GLP-1 na-arụ ọrụ na-akacha; Mgbe ọkwa glucose ọbara dị ala, mmetụta hyperglycemic nke onye na-anabata glucagon na-egbochi hypoglycemia.
(3) Usoro mmekọrịta
Mazdutide na-arụ ọrụ n'otu oge ma ndị na-anabata GLP-1 na ndị na-anabata glucagon. Ụzọ nrịbama nke ndị nnata abụọ a na-arụ ọrụ na-arụ ọrụ synergistically iji mee ka mmetụta nchịkwa metabolic dịkwuo ike ma dị ike. N'ihe gbasara ịbelata ibu, ịgbalite nnabata GLP-1 na-ebelata oriri ume site n'ịkwụsị agụụ na igbu oge iwepụta afọ, ebe nnabata glucagon na-akwalite mmefu ume. The synergistic omume nke ma ndị nnata ọzọ n'ụzọ dị irè nweta arọ Mbelata. N'ihe gbasara usoro glucose ọbara, mmetụta nke ọrụ nnabata abụọ ahụ na-akwado ibe ha iji nọgide na-enwe glucose n'ọbara n'ime oke nkịtị ma zere nnukwu mgbanwe.
3. Mmetụta Physiological
(1) Mmetụta Mbelata ibu
Ihe akaebe gbasara ụlọ ọgwụ: Ọtụtụ nnwale ụlọ ọgwụ egosila na Mazdutide nwere mmetụta mbelata ibu dị ukwuu. N'ọmụmụ ihe na-ezubere oke ibu ma ọ bụ ndị toro eto buru ibu na , 24 izu nke ọgwụgwọ Mazdutide (ya na oke dose nke 6 mg) butere oke ibu nke 6.7%-11.3%, ebe ndị otu placebo nwetara uru 1.0% dị arọ. N'ime otu dose dị iche iche, Mazdutide na 4.5 mg na 6 mg gosipụtara mmetụta mbelata nke ukwuu, yana ọdịiche ọgwụgwọ ma e jiri ya tụnyere placebo sitere na -7.7% ruo -12.3% (P <0.0001). Na nyocha nhazi na meta-analysis gụnyere ndị sonyere 680, Mazdutide gosipụtara uru dị ukwuu karịa placebo na mbelata ibu, yana ihe dị iche (MD) nke -6.22% (95% oge ntụkwasị obi [CI]: -8.02% na -4.41%).
Ọgụgụ 2 Ihe njedebe arụmọrụ ịdị arọ nke ahụ. mgbanwe Pasent site na ntọala na ịdị arọ ahụ n'izu 24. b Pasent mgbanwe site na ntọala na ibu ahụ n'oge.
(2) Mmetụta Iwu Glycemic
Mmetụta na ndị ọrịa nwere ụdị ọrịa shuga 2: Maka ndị ọrịa nwere ụdị ọrịa shuga 2, Mazdutide na-ebelata hemoglobin A1c (HbA1c) nke ọma na ọkwa glucose ọbara na-ebu ọnụ. N'ihe metụtara randomized, okpukpu abụọ, kpuru ìsì, placebo na-achịkwa usoro 2 nke ụlọ ọgwụ, ndị ọrịa nwere ụdị ọrịa shuga 2 nke natara ọgwụgwọ Mazdutide (na oke dose nke 6 mg) maka izu 20, gosipụtara nkezi mgbanwe na HbA1c sitere na -1.41% ruo -1.67%, ebe placebo otu gosipụtara mgbanwe nke 0 a statist (P) ma e jiri ya tụnyere 0.03% nke placebo. 0.0001). Ndị ọrịa ahụ nwetakwara mbelata dị ukwuu nke ịdị arọ ahụ, yana ngbanwe nke pasentị na-egosi mmekọrịta dabere na dose, ruru ruo -7.1%.
Uru dị na nhazi ọkwa glucose ọbara: Mazdutide abụghị naanị na-ebelata ọkwa glucose ọbara kamakwa ọ na-emezi mgbanwe nke glucose ọbara ma na-ebelata ohere nke ihe omume hypoglycemic. E jiri ya tụnyere ọgwụ antidiabetic ọdịnala, usoro agonist ya abụọ na-anabata ya na-enweta usoro glucose ọbara nke ọma na nke zuru oke, si otú a na-emeziwanye ndụ ndị ọrịa na ogologo oge.
(3) Mmetụta na ihe ngosi nke obi na nke metabolic
Usoro ọbara mgbali elu: Mazdutide na-ebelata ma systolic na diastolic ọbara mgbali. Nyocha usoro na meta-nyocha na-egosi na e jiri ya tụnyere placebo, Mazdutide na-ebelata ọbara mgbali systolic site na nkezi ọdịiche (MD) nke -7.57 mmHg (95% CI: -11.17 ka -3.98 mmHg); maka mbelata ọbara mgbali diastolic, MD bụ -2.98 mmHg (95% CI: -5.74 ruo -0.22 mmHg). Enwere ike ịsị na nke a sitere na ọtụtụ usoro Mazdutide, gụnyere imeziwanye ọrụ endothelial vaskụla, ibelata nguzogide vaskụla, na ịhazi nguzozi mmiri-sodium.
Iwu Lipid: Mazdutide na-ahazi profaịlụ lipid nke ọma. Ọ na-ebelata mkpokọta cholesterol (MD = -16.82%, 95% CI: -24.52 ruo -9.13%), triglycerides (MD = -43.29%, 95% CI: -61.57 to -25.01%), na obere njupụta lipoprotein (MD = -17.05.% . -2%): -2-9. ọkwa, ebe ọ na-arụkwa ọrụ ụfọdụ nchịkwa na lipoprotein dị elu (MD = -7.54%, 95% CI: -11.26 ka -3.83%). Mmetụta ndị a na-enyere aka belata ihe ize ndụ nke ọrịa obi ma nwee mmetụta nchebe na usoro obi obi.
(4) Mmetụta na hyperuricemia
Ihe akaebe nnwale anụmanụ: N'ihe ọmụmụ ụdị oke hyperuricemia (HUA), injection subcutaneous nke 0.05 mg/kg na 0.075 mg/kg nke Mazdutide (ụbọchị 3 ọ bụla) belatara ọkwa serum uric acid (SUA) na oke oke. E jiri ya tụnyere ndị otu HUA, SUA na serum creatinine (SCr) na-ebelata nke ukwuu na otu Maz-MD na Maz-HD, yana ọkwa protein urinary (U-Pro) belatara nke ukwuu na otu Maz-MD. Na mgbakwunye, Mazdutide kwalitere mgbanwe gbasara akụrụngwa gbasara akụrụ na oke HUA.
Ọgụgụ 3 a: Pasent mgbanwe site na ntọala n'ịdị arọ ahụ n'ime oge. b: Oke nke ndị sonyere na-erute ebumnuche ọnwụ ibu.
Nnyocha ngwa
(1) Ọganihu nnwale ụlọ ọgwụ
Ọnwụnwa ụlọọgwụ nke mbụ: Nnwale ụlọ ọgwụ izizi nke mbụ tụlere nchekwa, nnabata, na nrụpụta izizi nke Mazdutide. N'ime usoro a na-achịkwaghị achịkwa, nke a na-achịkwa placebo, ọtụtụ dose ịrị elu nke usoro 1b, ndị okenye buru oke ibu ma ọ bụ buru ibu ka a na-enye usoro dị iche iche nke Mazdutide (ruo 10 mg). Nsonaazụ gosiri na a nabatara Mazdutide nke ọma n'ime oke dose a, na-enweghị ihe ọjọọ dị njọ akọpụtara, yana nnukwu mbelata ibu.
Nnwale ụlọ ọgwụ nke 2: Nnwale ụlọ ọgwụ nke agba nke abụọ kwadoro ịdị mma na nchekwa nke Mazdutide n'ime ọnụ ọgụgụ dị iche iche. N'ime nnwale nke oge 2 nke ezubere iche maka ndị ọrịa China nwere ụdị ọrịa shuga 2, Mazdutide gosipụtara mmetụta dị ukwuu n'ibelata HbA1c na ịdị arọ ahụ, yana nchekwa dị ka ndị otu placebo. Mmeghachi omume ọjọọ ndị a na-emekarị bụ mmeghachi omume dị nro na nke na-adịghị ala ala, dị ka afọ ọsịsa na ọgbụgbọ. N'ime nnwale nke Phase 2 nke ezubere iche ndị okenye buru ibu ma ọ bụ buru oke ibu, izu 24 nke ọgwụgwọ Mazdutide (ruo 6 mg) gosipụtara ezigbo nrụpụta ịdị arọ na nchekwa.
(2) Ọmụmụ ihe atụnyere ọgwụ ndị ọzọ
Tụnyere GLP-1 agonists nnabata: Tụnyere omenala GLP-1 agonists, Mazdutide nwere ike inwe mmetụta dị ịrịba ama karịa na mbelata ibu na ụkpụrụ glucose ọbara n'ihi ịgbalite ya nke GLP-1 na ndị na-anabata glucagon. N'ime ọmụmụ ụfọdụ, Mazdutide nwetara oke ibu karịa ụfọdụ ndị na-anabata GLP-1 n'ime otu oge ọgwụgwọ wee gosipụta nkwụsi ike dị elu na njikwa glucose ọbara.
Tụnyere ọgwụ mgbochi ọrịa shuga ndị ọzọ: E jiri ya tụnyere ọgwụ mgbochi ọrịa ọnụ nke ọdịnala, Mazdutide abụghị naanị na-ebelata glucose ọbara n'ụzọ dị irè kamakwa ọ na-enyekwa uru ndị ọzọ dị ka mbelata ibu na imeziwanye ihe nrịbama metabolic nke obi.
Mmechi
Dị ka GLP-1/glucagon dual agonist, Mazdutide na-enweta usoro zuru oke nke metabolism ume, glucose ọbara, ọbara mgbali, na lipids ọbara site n'otu oge na-arụ ọrụ abụọ dị mkpa nke usoro nchịkwa metabolic, na-egosipụta mmetụta ọgwụgwọ zuru oke ma dị ike karịa otu agonists. Mazdutide nwere nkwa dị ukwuu maka ọrịa metabolic dị iche iche, gụnyere oke ibu, ụdị ọrịa shuga 2, na hyperuricemia.
Isi mmalite
[1] Zhang B, Cheng Z, Chen J, et al. Ịdị irè na nchekwa nke Mazdutide na ndị ọrịa China nwere ụdị ọrịa shuga 2: A Randomized, Double-kpuru, Plasebo-Controlled Phase 2 Trial[J]. Nlekọta ọrịa shuga, 2024,47 (1): 160-168.DOI: 10.2337 / dc23-1287.
[2] Nalisa DL, Cuboia N, Dyab E, et al. Ịdị irè na nchekwa nke Mazdutide na ọnwụ dị arọ n'etiti ndị na-arịa ọrịa shuga na ndị na-abụghị ndị ọrịa mamịrị: nyocha usoro na meta-analysis nke ule a na-achịkwaghị achịkwa [J]. Oke na Endocrinology, 2024,15. https://api.semanticscholar.org/CorpusID:267984513.
[3] Ji L, Jiang H, Cheng Z, et al. Usoro 2 na-achịkwa mazdutide na-achịkwa nke ọma na ndị okenye buru ibu nke China ma ọ bụ ndị okenye nwere oke ibu [J]. Nkwukọrịta okike, 2023,14 (1): 8289.DOI: 10.1038 / s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: A novel Glucagon-dị ka Peptide-1 (GLP-1R) na Glucagon (GCGR) Nnabata Dual Agonist, Mazdutide (IBI362), Attenuates Hyperuricemia na Hyperuric Rats[J]. Ọrịa shuga, 2023. https://api.semanticscholar.org/CorpusID:259452040
[5] Ji L, Gao L, Jiang H, et al. Nchekwa na ịdị irè nke GLP-1 na glucagon receptor dual agonist mazdutide (IBI362) 9 mg na 10 mg na ndị okenye China nwere oke ibu ma ọ bụ oke ibu: A na-achịkwaghị achịkwa, placebo-achịkwa, ọtụtụ-arịgoro-dose usoro 1b ikpe [J]. Eclinical ọgwụ, 2022,54:101691.DOI:10.1016/j.eclinm.2022.101691.
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