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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
Mazdutide bụ ọgwụ ọhụrụ na-arụ ọrụ dị ka agonist abụọ nke glucagon-dị ka peptide-1 (GLP-1) na ndị na-anabata glucagon. GLP-1 na ndị na-anabata glucagon na-arụ ọrụ dị mkpa na nhazi usoro metabolic na ahụ mmadụ. GLP-1 bụ mkpụrụ ndụ L nke dị na eriri afọ na-ezobe ya, na-ahapụ ya mgbe ọ risịrị nri, ma na-akpali mmepụta insulin n'ụzọ dabere na ntinye glucose ma na-egbochi secretion glucagon, si otú ahụ na-ebelata ọkwa glucose ọbara. GLP-1 na-ebelatakwa mkpofu afọ, na-abawanye satiety, ma na-ebelata iri nri, si otú a na-enye aka na njikwa ibu. Ndị na-anabata glucagon na-achịkwa nguzozi nke glucose ọbara. Mgbe glucagon jikọtara ya na onye na-anabata ya, ọ na-eme ka usoro ntụgharị mgbaàmà rụọ ọrụ iji kwalite glycogenolysis na gluconeogenesis, si otú ahụ na-abawanye ọkwa glucose ọbara. Mazdutide, dị ka onye na-eme ihe abụọ, na-enweta usoro nhazi nke metabolic site na usoro synergistic dị nkọ.
Usoro nke Omume
Usoro nchịkwa glucose ọbara
Na-akwalite secretion insulin: Mgbe ejikọtara ya na onye na-anabata GLP-1, Mazdutide na-arụ ọrụ ụzọ mgbama ala, gụnyere ụzọ akara cAMP-PKA. Ịgbalite ụzọ a na-eme ka uche nke mkpụrụ ndụ β-pancreatic dịkwuo elu na glucose, na-eduga n'ịchịkọta okwu mkpụrụ ndụ insulin na ụbara njikọ insulin na nzuzo. Mgbe ọkwa glucose ọbara na-ebili, Mazdutide nwere ike kpalite ntọhapụ insulin nke ọma, si otú a na-ebelata ọkwa glucose ọbara. N'ime ndị ọrịa nwere ụdị ọrịa shuga 2, Mazdutide na-abawanye mmepụta insulin postprandial site na usoro a, na-enyere aka ịnọgide na-enwe ọkwa glucose ọbara kwụsiri ike.
Mgbochi nke nzuzo glucagon: Omume Mazdutide na ndị na-anabata glucagon na-emetụtakwa nzuzo glucagon. Site na ijikọ ndị na-anabata glucagon, ọ na-egbochi ntụgharị mgbaàmà n'ime mkpụrụ ndụ α pancreatic, na-ebelata njikọ glucagon na ntọhapụ. Nke a na-egbochi glycogenolysis na gluconeogenesis, na-ebelata mmepụta glucose na isi iyi ma na-enyere aka n'ịbelata ọkwa glucose ọbara. Usoro nchikota nke insulin na glucagon na-enye Mazdutide nnukwu uru na nhazi nke glucose ọbara, na-eme ka njikwa ọkwa glucose ọbara dịkwuo mma ma na-ezere nnukwu mgbanwe.
Pasent mgbanwe site na ntọala na ibu ahụ ka oge na-aga. Ọnụọgụ ndị sonyere na-eru ebumnuche ịbelata ibu.
Usoro njikwa ibu
Usoro nchịkwa agụụ: Mazdutide na-ejikọta na ndị na-anabata GLP-1, na-arụ ọrụ neurons na ụlọ ọrụ nchịkwa agụụ hypothalamic. Neuron ndị a na-ekere òkè na mbufe akara satiety, na omume Mazdutide na-eme ka akara ngosi ndị a dịkwuo mma, si otú a na-ebelata oriri. Ọ nwekwara ike imetụta mpụta nke homonụ eriri afọ, dị ka ghrelin, na-achịkwa agụụ. N'ime ule ụlọ ọgwụ, ndị sonyere na-eji Mazdutide kwuru na agụụ belatara ma belata oriri nri kwa ụbọchị, na-eduga na mbelata ibu.
Ịba ụba ume ike: Mazdutide nwekwara ike ịkwalite ịbelata ibu site na imetụta metabolism ike nke ahụ. Nnyocha na-egosi na ọ nwere ike rụọ ọrụ anụ ahụ adipose agba aja aja, na-abawanye ọrụ thermogenic ya. Anụ ahụ adipose Brown bara ụba na mitochondria ma nwee ike iri ume site na thermogenesis na-adịghị ama jijiji. Mazdutide nwere ike ịhazi ụzọ mgbaàmà ndị metụtara ya iji kwalite ọdịiche na ịgbalite adipocytes agba aja aja, na-eme ka ikike thermogenic ha dịkwuo elu, si otú ahụ na-abawanye ike nke anụ ahụ na ịnweta ọnwụ. Mazdutide nwekwara ike imetụta metabolism nke anụ ahụ adipose na-acha ọcha, na-akwalite ntụgharị nke abụba ọcha ka ọ bụrụ abụba aja aja, na-emeziwanye metabolism abụba na ibelata mkpokọta abụba.
Usoro nhazi nke uric acid
Usoro okwu mkpụrụ ndụ ihe nketa: N'ime ọmụmụ ihe na-eji ụdị oke hyperuricemia, mgbanwe dị ịrịba ama na nkwupụta nke mkpụrụ ndụ ihe nketa ụfọdụ ka a hụrụ na-esochi ntinye aka Mazdutide. Mgbanwe ndị a na okwu mkpụrụ ndụ ihe nketa nwere ike nweta mbelata ọkwa uric acid site na ịhazi ihe mmalite nke njikọ uric acid yana isonye na usoro dị ka metabolism glycolipid na metabolism purine. Mkpụrụ ndụ ihe nketa na-akwalite mkpochapụ uric acid ma ọ bụ sonye na ụzọ metabolic nke na-egbochi njikọ uric acid, ebe mkpụrụ ndụ ihe nketa na-ebelata njikọ nke ndị na-ebute ụzọ maka njikọ uric acid, si otú ahụ na-ebelata ọkwa nke uric acid n'ụzọ zuru ezu.
Usoro usoro ụzọ metabolic: Nnyocha nke renal transcriptomics kpughere na ntinye aka nke Mazdutide mere ka ụzọ KEGG dịkwuo mma gụnyere secretion bile, renin-angiotensin system, histidine metabolism, platinum resistance, hematopoietic cell lineages, complement, and coagulation cascade. Ịchịkwa ụzọ ndị a nwere ike imetụta metabolism uric acid na-apụtaghị ìhè. Iwu nke ụzọ nzuzo nke bile nwere ike imetụta metabolism nke bile acid, nke nwere njikọ chiri anya na metabolism lipid. Mgbanwe na metabolism lipid nwere ike n'aka nke ya na-emetụta mmepụta na mkpochapụ uric acid. Ịchịkwa usoro renin-angiotensin nwere ike imetụta hemodynamics gbasara akụrụ na ọrụ tubular, si otú ahụ na-emetụta uric acid reabsorption na excretion.
Ịrụ ọrụ
Mmetụta nchịkwa glucose
N'ime usoro nyocha ụlọ ọgwụ na-enweghị usoro, nke kpuru okpukpu abụọ, ebe a na-achịkwa placebo na ndị ọrịa nwere ụdị ọrịa shuga 2, Mazdutide gosipụtara mmetụta nchịkwa glucose ọbara dị ukwuu. Ọmụmụ ihe ahụ kenyere ndị okenye nwere ụdị ọrịa shuga 2 na-enweghị usoro ịnata 3 mg, 4.5 mg, ma ọ bụ 6 mg nke Mazdutide, 1.5 mg nke dulaglutide mepere emepe, ma ọ bụ placebo, ma na-enye injections subcutaneous maka izu 20. Nsonaazụ gosiri na site na ntọala ruo izu 20, mgbanwe mgbanwe dị na hemoglobin A1c (HbA1c) na ndị otu Mazdutide sitere na -1.41% ruo -1.67%, ebe otu dulaglutide nwere mgbanwe -1.35% na placebo otu nwere mgbanwe nke 0.03%. E jiri ya tụnyere otu placebo, mgbanwe dị na ọkwa HbA1c n'ime otu dose Mazdutide niile dị ịrịba ama (P <0.0001 niile). Nke a na-egosi na Mazdutide dị irè nke ukwuu karịa placebo na mbelata ọkwa HbA1c na ndị ọrịa nwere ụdị ọrịa shuga 2, yana atụnyere ma ọ bụ karịa dulaglutide. Mbelata ọkwa HbA1c na-egosipụta ikike Mazdutide iji meziwanye njikwa glycemic ogologo oge na ndị ọrịa, si otú a na-ebelata nsogbu nke ọrịa shuga na-adịghị ala ala.
Mmetụta mbelata ibu
Mazdutide na-egosipụta nrụpụta dị ukwuu na njikwa ibu. N'ọmụmụ ihe ezubere iche maka oke ibu ma ọ bụ ndị okenye buru ibu, izu 24 nke ọgwụgwọ Mazdutide gosipụtara mmetụta dị mma na-efunahụ ibu. Ndị okenye buru oke ibu (nchịkọta anụ ahụ [BMI] ≥24 kg / m²) na polyphagia na / ma ọ bụ opekata mpe otu nsogbu metụtara oke ibu, ma ọ bụ ndị okenye buru ibu (BMI ≥28 kg / m²), A na-ekenye ya na-enweghị usoro (3: 1: 3: 1: 3: 1) iji nata 3mgzdu kwa izu, 5mgzdu ma ọ bụ 6mg. ọgwụgwọ. Nsonaazụ gosiri na site na ntọala ruo izu 24, mgbanwe mgbanwe pasentị dị na ịdị arọ bụ -6.7% (njehie ọkọlọtọ 0.7) na Mazdutide 3 mg otu, -10.4% (0.7) na 4.5 mg otu, -11.3% (0.7) na 6 mg otu, na 1.0% na place (0.7) otu. E jiri ya tụnyere placebo, ọdịiche ọgwụgwọ maka Mazdutide n'ofe ụdị ọgwụ niile sitere na -7.7% ruo -12.3% (niile P <0.0001). Nke a na-egosi na Mazdutide nwere ike ibelata ibu ahụ na oke ibu ma ọ bụ buru oke ibu n'ụzọ dabere na dose. Mbelata ibu a abụghị naanị na-enyere aka melite ọdịdị anụ ahụ nke ndị ọrịa mana nke ka mkpa na-ebelata ohere nke ọrịa dị iche iche metụtara oke ibu, dị ka ọrịa obi na akwara ozi na ọrịa shuga.
Uric acid na-ebelata mmetụta
N'ụdị oke nke hyperuricemia, Mazdutide gosipụtara mmetụta dị mma na-ebelata uric acid. A kpalitere hyperuricemia n'ime oke site na nchịkwa ọnụ nke adenine na potassium oxinic acid, na-esote ọgwụgwọ na usoro dị iche iche nke Mazdutide. Nsonaazụ gosiri na otu Mazdutide nke ọkara na nke dị elu (0.05 mg/kg na 0.075 mg/kg, nke a na-enye site na ntụtụ subcutaneous kwa ụbọchị 3) belatara ọkwa serum uric acid (SUA) na oke. Mazdutide mekwara ka ọrụ akụrụ dịkwuo mma, belata ọkwa serum creatinine (SCr) na protein mmamịrị (U-Pro), yana imeziwanye pathology anụ ahụ gbasara akụrụ. Nke a na-egosi na Mazdutide abụghị naanị ibelata ọkwa uric acid serum mana ọ nwekwara mmetụta nchebe megide mmebi akụrụ nke hyperuricemia kpatara.
Mpaghara Ngwa
Ọgwụgwọ nke ụdị ọrịa shuga 2
Nyere uru Mazdutide dị na njikwa glucose ọbara, ọ nwere nnukwu ikike itinye n'ọrụ na ọgwụgwọ ụdị ọrịa shuga 2. Ka ọ dị ugbu a, ọgwụgwọ ụdị ọrịa shuga nke abụọ na-adabere na nchikota ọtụtụ ọgwụ iji chịkwaa ọkwa glucose ọbara na igbochi omume nke nsogbu. Dịka agonist dual receptor agonist, usoro pụrụ iche nke Mazdutide na-enyere ya aka ịhazi glucose metabolism n'ọtụtụ ọkwa, na-enye nhọrọ ọgwụgwọ ọhụrụ maka ndị ọrịa nwere ụdị ọrịa shuga 2. Tụnyere ọgwụ antidiabetic ọdịnala, Mazdutide abụghị naanị na-ebelata ọkwa glucose ọbara nke ọma kamakwa ọ na-enyekwa uru nke mbelata ibu, nke dị mkpa karịsịa maka ọtụtụ ndị ọrịa nwere ụdị ọrịa shuga 2 bụ ndị buru oke ibu ma ọ bụ buru ibu.
Oke oke ibu na njikwa oke ibu
Oke ibu na oke ibu aghọwo ihe gbasara ahụike ọha na eze zuru ụwa ọnụ na mmalite nke ọrịa dị iche iche na-adịghị ala ala. Mmetụta dị ịrịba ama nke Mazdutide na njikwa ibu na-eme ka ọ bụrụ nhọrọ ọgwụgwọ maka ndị buru oke ibu na ndị buru ibu. Site n'ịchịkwa agụụ na ịba ụba ume ike, Mazdutide nwere ike inyere ndị ọrịa buru ibu na oke ibu aka ịkwụsị ibu ma melite ọnọdụ metabolic ha. Tụnyere usoro ịbelata ibu dị ka nri nri na mmega ahụ, Mazdutide na-enye nhọrọ ọgwụgwọ mgbakwunye dị irè karị, ọkachasị maka ndị na-agbasi mbọ ike iru oke ibu ha site na mmemme ndụ. Na mgbakwunye, n'ihi usoro omume ya gụnyere ọtụtụ usoro nchịkwa physiological, Mazdutide nwere ike inwe mmetụta dị mma na sistem obi na sistem metabolic ka ọ na-ebelata ibu, si otú a na-ebelata ihe ize ndụ nke nsogbu ndị metụtara oke ibu.
Mmechi
Na nchịkọta, dị ka akwụkwọ akụkọ dual agonist nke GLP-1 na ndị na-anabata glucagon, Mazdutide na-egosiputa usoro omume pụrụ iche na nrụpụta dị ukwuu na nhazi nke glucose ọbara, njikwa ibu, na ikike nke uric acid, na-arụ ọrụ dị mkpa na njikwa ụdị ọrịa shuga 2, oke ibu, na oke ibu.
Isi mmalite
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[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.semanticcholar.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
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