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Akụkọ niile na ozi ngwaahịa 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.
N'ụwa niile, oke ibu aghọwo ihe na-arịwanye elu nke ahụike ọha na eze, jikọtara ya na ọrịa dị iche iche na-adịghị ala ala dị ka ọrịa obi na ọrịa shuga 2, na-eme ka ịchọta ụzọ dị irè dị arọ isi na-elekwasị anya na nyocha ahụike. Survodutide, dị ka ọgwụ ọhụrụ, egosipụtala ịdị irè na mbelata ibu.
Nkọwa nke Survodutide
Survodutide bụ nyocha nke na-eme ogologo oge na-eme agonist nke na-eme n'otu oge na-elekwasị anya na onye na-anabata glucagon-dị ka peptide-1 (GLP-1R) na onye na-anabata insulinotropic polypeptide na-adabere na glucose (GIPR). Ọ na-achọ naanị nchịkwa otu ugboro kwa izu, na-enye ndị ọrịa ohere ka ukwuu ma na-emeziwanye nnabata na ọgwụgwọ ogologo oge.
Usoro nke Survodutide na mbelata ibu
Na-achịkwa oriri ike
Mbelata agụụ: Mgbe ịgbalite GLP-1R na GIPR, Survodutide na-emekọrịta ihe na sistemụ ụjọ nke etiti iji hazie ebe njikwa agụụ hypothalamic. Ntinye nke GLP-1R na-arụ ọrụ na eriri vagal afferent iji nyefee akara na arcuate nucleus nke hypothalamus, na-egbochi ọrụ nke agrep protein (AgRP) neurons, Ọ nwekwara ike rụọ ọrụ neurons proopiomelanocortin (POMC), si otú ahụ na-akpali mmetụta nke satiety na ibelata nri. Ịgbalite GIPR n'ọrụ nwekwara ike welie mmetụta a na-egbochi agụụ site na ụzọ akwara ndị yiri ya ma ọ bụ synergistic, si otú a na-ebelata ọchịchọ anụ ahụ maka nri ma na-ebelata oriri ume.
Ịgbanwe mmasị nri: N'ụdị hamster nke oke ibu na dyslipidemia kpatara site na nri nhọrọ efu, Survodutide gosipụtara mmetụta pụrụ iche na mmasị nri. E jiri ya tụnyere ndị na-ahụ maka njikwa, Survodutide na-ebelata nke ukwuu oriri nke nnukwu abụba na mmiri fructose n'ime oge ọgwụgwọ nke izu 5, ebe ọ na-enweghị mmetụta doro anya na oriri nke nri mgbe niile na mmiri nkịtị. Mmetụta nchịkwa a na nhọrọ nri na-enyere aka belata oriri nke calorie dị elu, na-achịkwa nchịkọta ike dị ukwuu na isi iyi ya na ịtọ ntọala maka ịbelata ibu.
Na-achịkwa mmefu ike
Na-akwalite abụba oxidation: Survodutide na-egosipụta mmetụta nchịkwa dị mkpa na metabolism abụba. Site na ịgbalite GLP-1R na GIPR, ọ na-emetụta metabolism abụba site na ọtụtụ ụzọ mgbaàmà. Ọ na-akwalite lipolysis n'ime adipocytes, na-abawanye ntọhapụ nke fatty acids; A na-ebuga fatty acids ndị a ewepụtara na mitochondria maka oxidation, si otú a na-abawanye mmefu ike. Nnyocha egosiwo na n'ime ụdị adipocyte in vitro, na-agbaso ọgwụgwọ Survodutide, enzymes isi na-etinye aka na lipolysis na fatty acid oxidation, dị ka hormone-sensitive lipase (HSL), carnitine palmitoyltransferase-1 (CPT-1), na-egosi na usoro ya na-eme n'ịkwalite abụba oxidation gụnyere ịhazi enzymes isi na metabolism abụba.
Ịba ụba ike mmefu: Na mgbakwunye na ime ihe ozugbo na mkpụrụ ndụ abụba iji kwalite oxidation abụba, Survodutide nwekwara ike ịbawanye mmefu ume site na imetụta metabolism ike sistemu. Na nnwale anụmanụ, a hụrụ na ọ bụ ezie na ọkwa ọrụ nke ụmụ anụmanụ agbanweghị nke ọma mgbe nchịkwa Survodutide gasịrị, ọnụego metabolic basal ha mụbara. Nke a bụ n'ihi mmetụta zuru oke nke ọgwụ ahụ na ọtụtụ anụ ahụ na akụkụ ahụ, na-eme ka ọrụ metabolic dị na imeju na anụ ahụ skeletal, si otú ahụ na-abawanye oriri ike na ọnọdụ izu ike ma nweta ụkọ ume, nke na-akwalite nkwụsị arọ.
Nhazi nke metabolism metabolism na insulin sensitivity
Imelite nguzogide insulin: Ndị ọrịa buru ibu na-enwekarị nguzogide insulin, nke na-emetụta metabolism ike nkịtị na itinye n'ọrụ. Survodutide na-arụ ọrụ GLP-1R na-akpali mmepụta insulin ka ọ na-eme ka mmetụta insulin dịkwuo elu, si otú ahụ na-amụba nzaghachi anụ ahụ na insulin. N'ime ọmụmụ nke ndị ọrịa nwere ụdị ọrịa shuga 2, mgbe izu 16 nke ọgwụgwọ Survodutide gasịrị, ọkwa insulin plasma na insulin resistance index (HOMA-IR) belatara nke ukwuu, na-egosi na ọgwụ ahụ nwere ike melite nguzogide insulin, na-eme ka nnabata cellular ka mma na iji glucose, na-ebelata ntụgharị ya na abụba, yana inye aka na njikwa ibu.
Na-achịkwa ọkwa glucose ọbara: Survodutide's dual agonist agonist na-enye ya uru pụrụ iche n'ịhazi ọkwa glucose ọbara. GLP-1R na-akwalite mmepụta insulin ma na-egbochi mwepụta glucagon, si otú a na-ebelata ọkwa glucose ọbara. Agonism GIPR na-akwalite mmepụta insulin n'okpuru ọnọdụ anụ ahụ. Site na mmetụta synergistic, ọ nwere ike idobe ọkwa glucose ọbara kwụsie ike. Ọkwa shuga dị n'ọbara kwụsiri ike na-enyere aka belata agụụ na ụbara nchekwa ike nke mgbanwe shuga ọbara kpatara, na-egosipụta mmetụta dị mma na njikwa ibu n'ụzọ na-apụtaghị ìhè.
Ọrụ Survodutide na mbelata ibu
Mmetụta ọnwụ dị oke mkpa: N'ime usoro nyocha ọnụọgụ ọnụọgụ abụọ, nke a na-achịkwa nke abụọ, placebo na-achịkwa ndị ọrịa buru ibu, ndị okenye 387 dị afọ 18-75 nwere ihe nrịbama ahụ (BMI) ≥27 kg / m² na enweghị ọrịa shuga ka enyere ndị otu ise na-enweghị usoro, na-anata injections subcutaneous kwa izu nke Survodutide (0.6, 2.4, 3.6, ma ọ bụ 4.8 mg) ma ọ bụ placebo maka oge ọgwụgwọ izu 46. Nsonaazụ gosiri na n'ime izu 46, ndị ọrịa na-agwọ 4.8 mg nke Survodutide nwetara nkezi ibu arọ nke 18.7% ma e jiri ya tụnyere otu placebo, yana ọdịiche dị ịrịba ama na mbelata ibu. N'ọmụmụ ihe ọzọ ezubere iche maka ndị ọrịa nwere ụdị ọrịa shuga 2 na oke ibu, ọgwụgwọ Survodutide mere ka mbelata ịdị arọ nke dabere na dose mgbe izu iri na isii gachara, yana mbelata kacha nke 8.7%. Na mgbakwunye, Survodutide na dose nke ≥1.8 mg otu ugboro kwa izu na-emepụta oke ibu karịa GLP-1 agonist receptor Semaglutid, nke butere mbelata ibu nke 5.3%.
Ọdịiche nwoke na nwanyị na BMI: Ntụle ndị ọzọ n'otu n'otu gosiri na mmetụta mwepu nke Survodutide dịgasị iche n'ofe nwoke na nwanyị na ọkwa BMI dị iche iche. N'ime ule ahụ e kwuru n'elu na-elekwasị anya na ndị ọrịa buru ibu, na izu 46, nkezi pasent nke ọnwụ (17.0%) na 4.8 mg Survodutide otu dị elu karịa ụmụ nwanyị karịa ụmụ nwoke (11.9%); n'ofe mpaghara BMI dị iche iche, ndị ọrịa nwere BMI <30 kg / m² nwere pasentị ọnwụ dị elu dị elu (19.1%), mana ụkpụrụ ọnwụ zuru oke adịchaghị iche n'ofe otu obere BMI. Nke a na-egosi na na omume ụlọ ọgwụ, ndị dọkịta nwere ike ịkọwa n'ụzọ ziri ezi na mmetụta ọnwụ nke Survodutide dabere na ihe ndị dị ka nwoke na nwanyị ọrịa na BMI.
Nkesa abụba anụ ahụ yana nkwalite metabolic
Mbelata abụba visceral: Survodutide abụghị naanị na-ebelata oke ahụ mana ọ nwekwara mmetụta dị mma na nkesa abụba anụ ahụ. Nnukwu mkpokọta abụba visceral nwere njikọ chiri anya na mmepe nke ọrịa metabolic dị iche iche. N'ime ọmụmụ ihe dị mkpa, mgbe ha natachara ọgwụgwọ Survodutide ruo oge ụfọdụ, ndị ọrịa nwetara mbelata dị ukwuu na mpaghara abụba visceral. Nke a bụ n'ihi na ọgwụ ahụ na-akwalite mmebi na oxidation nke abụba visceral, na-emeziwanye metabolism ya ma si otú ahụ belata ihe ize ndụ nke metabolic metụtara oke abụba visceral.
Na-emeziwanye ihe na-adịghị mma nke egbugbere ọnụ: Ndị ọrịa buru oke ibu na-enwekarị ọrịa lipid, dị ka hypercholesterolemia na hypertriglyceridemia. Survodutide ọ bụghị naanị na-enyere aka n'ịbelata ibu, kamakwa ọ na-eme ka usoro lipid dịkwuo mma. Na nnwale anụmanụ, hamsters buru ibu ejiri Survodutide gosipụtara mbelata dị ukwuu na mkpokọta cholesterol mkpokọta plasma, yana mbelata 41% na otu Survodutide yana mbelata 24% na otu semaglutide. Achọpụtara nsonaazụ ndị yiri ya na ule mmadụ, ebe ọgwụgwọ Survodutide mere ka mbelata dị ukwuu na ọkwa triglyceride. O nwekwara mmetụta dị iche iche nke usoro nchịkwa na cholesterol lipoprotein dị obere (LDL-C) na cholesterol dị elu (HDL-C), na-enyere aka dozie dyslipidemia ma belata ihe ize ndụ nke ọrịa obi.
Mmetụta na ihe ize ndụ nke obi
Mbelata ọbara mgbali: oke ibu bụ otu n'ime isi ihe na-ebute ọbara mgbali elu. N'ime ule ụlọ ọgwụ na-ezubere ndị ọrịa buru ibu, mgbe izu 46 nke ọgwụgwọ Survodutide gasịrị, ma ọbara mgbali systolic (SBP) na ọbara mgbali elu diastolic (DBP) gosipụtara mbelata dị ukwuu. E jiri ya tụnyere ndị otu placebo, otu 4.8 mg Survodutide gosipụtara mbelata kachasị elu nke 10.2 mmHg na SBP na 4.8 mmHg na DBP. Mmetụta mbelata ọbara a nwere ike jikọta ya na ọtụtụ ihe, gụnyere mmụba nke Survodutide nke ọrụ endothelial vaskụla, mbelata ọrụ akwara ọmịiko, na oke ibu, nke na-enyere aka belata ohere nke ọrịa obi.
Ịkwalite ọrụ vaskụla: Survodutide nwekwara ike ịmepụta mmetụta nchebe na usoro obi site na imeziwanye ọrụ nke sel endothelial vaskụla. Na-esote nchịkwa Survodutide, ntọhapụ nke nitric oxide (NO) site na sel endothelial vaskụla na-abawanye. Ọ dịghị bụ vasodilator dị mkpa nke na-eme ka arịa ọbara gbasaa, na-ebelata nkwụsị nke vaskụla, na-eme ka mgbasa ọbara dịkwuo mma. Ọgwụ ahụ nwekwara ike igbochi nzaghachi mkpali na nrụgide oxidative, si otú ahụ belata mmebi mgbidi vaskụla ma nọgide na-enwe ahụ ike vaskụla.
Ngwa nke Survodutide na mbelata ibu
Ndị Ezubere iche
Ndị buru ibu na oke ibu: Maka ndị buru oke ibu ma ọ bụ ndị buru oke ibu nwere BMI ≥ 27 kg / m², Survodutide egosipụtala mmetụta dị oke ibu dị arọ. Ma ndị ọrịa nwere oke ibu dị mfe yana ndị nwere oke ibu na-esonyere nsogbu metabolic ndị ọzọ dị ka ụdị ọrịa shuga 2 ma ọ bụ dyslipidemia nwere ike irite uru na ọgwụgwọ Survodutide. N'ime ule ụlọ ọgwụ, ndị ọrịa buru ibu gafee afọ dị iche iche (18-75 afọ) gosipụtara nzaghachi dị mma na Survodutide, na-egosi ọnụ ọgụgụ dị ukwuu nke ndị ruru eru.
Ndị ọrịa nwere oke ibu metụtara ọrịa a kapịrị ọnụ: Na mgbakwunye na ọnụ ọgụgụ buru ibu n'ozuzu, Survodutide bụkwa nhọrọ ọgwụgwọ maka oke ibu nke ọrịa ndị akọwapụtara, dị ka polycystic ovary syndrome (PCOS), ebe oke ibu na nsogbu metabolic na-ebikọ ọnụ.
Iji nwetakwuo mmetụta ọnwụ ọnwụ ma melite ọnọdụ metabolic, enwere ike iji Survodutide na usoro ọgwụgwọ ndị ọzọ. Mgbe ejikọtara ya na usoro ndụ ndụ (nchịkwa nri na mmega ahụ), enwere ike nweta mmetụta synergistic. N'ime ule ụlọ ọgwụ, ndị ọrịa natara ọgwụgwọ Survodutide jikọtara na mmega ahụ mgbe niile na nri kwesịrị ekwesị na-enweta oke ibu ibu yana mmụba dị ịrịba ama na ihe nrịbama metabolic. Na mgbakwunye, maka ndị ọrịa nwere ụdị ọrịa shuga 2 na oke oke ibu, enwere ike iji Survodutide yana ọgwụ mgbochi ọrịa shuga ndị ọzọ dị ka metformin iji chịkwaa ọkwa shuga dị n'ọbara ka ị na-enweta njikwa ibu ka mma.
Mmechi
Na nchịkọta, Survodutide, dị ka onye na-anabata ihe na-anabata ihe abụọ, bara uru maka ịbelata ibu. Usoro ọrụ ya pụrụ iche ọ bụghị nanị na-ebelata ibu nke ọma kamakwa ọ na-eme ka nkesa abụba dị mma, na-achịkwa glucose na metabolism lipid, ma na-ebelata ihe ize ndụ nke obi.
Isi mmalite
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[2] Le Roux C, Steen O, Lucas KJ, et al. Survodutide, onye na-anabata glucagon / GLP-1 (GCGR/GLP-1R) abụọ agonist, na-eme ka usoro cardiometabolic dị na ndị okenye nwere oke ibu: nyocha nke ebe a na-achịkwa placebo, usoro 2 na-enweghị usoro [J]. Akwụkwọ akụkọ obi European, 2024,45 (Mgbakwunye_1):ehae666-ehae2895.DOI:10.1093/eurheartj/ehae666.2895.
[3] Blüher M, Rosenstock J, Hoefler J, et al. Mmetụta nzaghachi dose na HbA (1c) na mbelata ahụ nke survodutide, onye na-anabata glucagon/GLP-1, ma e jiri ya tụnyere placebo na semaglutide mepere emepe na ndị nwere ụdị ọrịa shuga 2: nnwale ụlọ ọgwụ na-enweghị usoro [J]. Diabetologia, 2024,67 (3): 470-482.DOI: 10.1007/s00125-023-06053-9.
[4] Mei Z, Pu J, Shao Z. Ọnwụnwa abụọ nke ọgwụgwọ maka MASH na imeju Fibrosis [J]. Akwụkwọ akụkọ New England nke Medicine, 2024,391 (15): 1461-1462.DOI: 10.1056 / NEJMc2411003.
[5] Sanyal AJ, Bedossa P, Fraessdorf M, et al. Ọnwụnwa nke Survodutide na MASH na Fibrosis[J]. Akwụkwọ akụkọ ọgwụ New England, 2024,391 (4): 311-319.DOI: 10.1056 / NEJMoa2401755.
[6] Le Roux CW, Steen O, Lucas KJ, et al. Glucagon na GLP-1 agonist dual agonist survodutide maka oke ibu: a randomized, okpukpu abụọ kpuru, placebo-achịkwa, dose-achọpụta usoro 2 ikpe.[J]. Lancet. Ọrịa shuga mellitus & Endocrinology, 2024. https://api.semanticscholar.org/CorpusID:267503510
[7] Lawitz EJ, Fraessdorf M, Neff GW, et al. OS-119 Survodutide (BI 456906), onye na-anabata glucagon / glucagon-dị ka peptide-1 agonist (GCGR/GLP-1R) dual agonist, na ndị nwere ụgwọ ọrụ na decompensated cirrhosis: a multinational, open-label, phase 1 trial[J]. Akwụkwọ akụkọ gbasara ịba ọcha n'anya, 2024. https://api.semanticscholar.org/CorpusID:270457365
[8] Le Roux CW, Steen O, Lucas KJ, et al. 6926 Subgroup Analysis by Gender and Body Mass Index (BMI) na ndị mmadụ bi na oke ibu/oke ibu na Survodutide, Glucagon/GLP-1 Nnabata Dual Agonist, Phase II Trial[J]. Akwụkwọ akụkọ nke Endocrine Society, 2024,8 (Mgbakwunye_1): bvae133-bvae163.DOI:10.1210/jendso/bvae163.033.
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