Retatrutide (GLP-3) 20 mg

▎ Ọdịdị Retatrutide

Isi mmalite: PubChem

Usoro: YA⊃1;QGTFTSDYSI-L⊃2;LDKK⁴AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Ụdị mkpụrụ ndụ: C 221H 342N 46O68 Arọ molekụla: 4731 g/mol Nọmba CAS: 2381089-83-2 PubChem CID: 171390338 Ndị otu: LY3437943

▎ Nnyocha Retatrutide

Kedu ihe ndabere nyocha nke Retatrutide?

Nchọpụta nyocha nke Retatrutide nwere njikọ chiri anya na nsogbu zuru ụwa ọnụ na-arịwanye elu nke oke ibu na metabolism, yana njedebe nke ọgwụ ọgwụgwọ dị ugbu a: oke ibu na metabolism na-ebute ahụike ọha na eze, yana ọnụ ọgụgụ oke ibu zuru ụwa ọnụ ga-eru ijeri 4.005 site na 2035 yana ọnụ ọgụgụ nke ndị ọrịa metabolism na-abawanye ruo nde 592, na-akpata metabolism dị ukwuu. Multi-ledge receptor agonist peptides apụtala dị ka ihe ngwọta, nke nwere ike igbochi oke ibu, na-agwọ ọrịa metabolism, na izere mmetụta ndị na-egbu egbu nke ọgwụ ndị dị adị, na-eme ka ha bụrụ usoro na mmepe nke oke ibu na ọgwụgwọ metabolism.

Kedu ihe bụ usoro nke Retatrutide?

Na-achịkwa metabolism ike site na ịgbalite multi-receptor

Retatrutide bụ agonist atọ na-anabata ihe na-elekwasị anya na glucose dabere insulinotropic polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), na glucagon receptor (GCGR). Ọ n'out oge activates ndị a atọ anabata, na-achịkwa ike metabolism site multiple ụzọ.

GIPR agonist ọrụ: 

GIP bụ hormone na-ezobe insulin nke eriri afọ nke mkpụrụ ndụ eriri afọ K na-ewepụta ma wepụta ya mgbe nri gasịrị. Retatrutide na-eme ka GIPR rụọ ọrụ, na-akwalite mmepụta insulin, na-eme ka mmetụta insulin dịkwuo elu, ma si otú a na-enyere ahụ ahụ aka ịmịkọrọ ma jiri glucose mee ihe nke ọma, si otú a na-ebelata ọkwa glucose ọbara. Na mgbakwunye, GIP nwere ike imetụta metabolism abụba site na ịhazi ọrụ adipocyte na ibelata mkpokọta abụba ^[1].

Ọrụ agonist GLP-1R: 

GLP-1 bụ homonụ peptide nke sel intestinal L na-emepụta. Mgbe ịgbalite GLP-1R, Retatrutide na-emepụta mmetụta bara uru dị iche iche. Ọ nwere ike kpalite mmepụta insulin n'ụzọ dabere na mkpokọta glucose, si otú a na-ebelata ọkwa shuga dị n'ọbara. Ọ nwere ike igbu oge mkpofu afọ, mụbaa satiety, ma belata oriri. GLP-1R agonism nwekwara ike na-arụ ọrụ na Central ụjọ usoro, na-achịkwa agụụ na ume itule, si otú na-enyere aka na ibu ibu ^[2].

Mmetụta GCGR agonist: 

Glucagon na-abawanye ọkwa glucose ọbara, mana n'okpuru mmetụta nke Retatrutide, agonism GCGR na-emepụta mmetụta dị iche iche. Ọ na-akwalite glycogenolysis na gluconeogenesis na imeju. N'okpuru mmetụta jikọtara ọnụ nke Retatrutide, anụ ahụ anaghị enwe mmụba dị mfe na ọkwa glucose ọbara kama kama ọ na-achịkwa metabolism ike iji mee ka mgbari abụba dịkwuo elu, si otú ahụ na-enweta ibu ibu na mma metabolism. GCGR agonism nwekwara ike imetụta metabolism lipid imeju, na-ebelata mkpokọta abụba imeju ^[3].

Mmetụta na Usoro Ọrịa shuga metụtara Ọrịa shuga

Site n'ime otu oge na ndị nnata atọ ahụ a kpọtụrụ aha, Retatrutide na-emetụta ọtụtụ usoro physiological metụtara metabolism.

Usoro nchịkwa glucose ọbara: 

Site n'ịgbalite GIPR na GLP-1R iji kwalite mmepụta insulin, yana ịhazi GCGR nke ọma, Retatrutide nwere ike belata ọkwa glucose ọbara. A na-akpọ mmetụta hypoglycemic ya mgbe ọkwa glucose ọbara dị elu, ebe o yighị ka ọ ga-ebute hypoglycemia mgbe glucose ọbara dị mma, nke bara uru maka njikwa glucose ọbara n'ime ndị ọrịa nwere ọrịa shuga ^..

Njikwa ibu: 

Retatrutide na-egosipụta nrụpụta dị ukwuu na njikwa ibu. Site na ịgbalite GLP-1R, ọ na-ebelata mkpofu afọ, na-abawanye satiety, ma na-ebelata oriri; site n'ịchịkwa abụba metabolism, ọ na-akwalite mmebi abụba na mmefu ume, si otú a na-enweta ibu ibu. Nnwale ụlọ ọgwụ egosila na ndị ọrịa buru oke ibu ma ọ bụ ndị buru oke ibu na Retatrutide na-enweta oke ibu dị arọ n'ime oge ụfọdụ ^[5,6].

Usoro Lipid: 

Ọgwụgwọ retatrutide na-eme ka profaịlụ lipid ndị ọrịa dịkwuo mma. Ọ na-ebelata triglyceride (TG), cholesterol lipoprotein dị obere (LDL-C), yana oke lipoprotein cholesterol (VLDL-C) dị obere, na-achịkwa apolipoproteins, dị ka iweda apolipoprotein B (apoB) na apolipoprotein C -III (apoC-by) na-ebelata ọkwa nke lipoproteins, na-ebelata ọnụ ọgụgụ lipoproteins nke lipoproteins, na-ebelata ọnụ ọgụgụ lipoproteins nke lipoproteins. na-akwalite ahụ ike obi ^[7].

Melite metabolism lipid imeju: 

Maka ndị ọrịa nwere ọrịa imeju na-adịghị egbu egbu (NAFLD) jikọtara ya na dysfunction metabolic, Retatrutide na-ebelata nke ukwuu ọdịnaya abụba imeju. N'ime ule ụlọ ọgwụ dị mkpa, ndị ọrịa na-eji ọgwụ dị iche iche nke Retatrutide gosipụtara mbelata nke ukwuu na abụba imeju ma e jiri ya tụnyere ntọala, na-egosi na Retatrutide nwere mmetụta nchịkwa dị mma na metabolism abụba imeju, nke bara uru maka imezi ọrụ imeju ^[3]..

Ọgụgụ 1 Usoro nke Retatrutide ^[8].

Kedu ihe bụ ngwa Retatrutide?

Ọgwụgwọ oke ibu: 

Ibu ibu aghọwo isi okwu ahụike ọha na eze zuru ụwa ọnụ, jikọtara ya na mmalite na ọganihu nke ọrịa dị iche iche na-adịghị ala ala. Retatrutide egosipụtala arụmọrụ dị ukwuu na ọgwụgwọ oke ibu. Ndị ọrịa buru ibu ejiri Retatrutide gwọọ ha nwetara mbelata pụtara ìhè na ịdị arọ ahụ. N'ime izu 48 nke ọmụmụ oke ibu nke Phase 2, ndị ọrịa na-emeso 8mg na 12mg nke Retatrutide nwetara mbelata ịdị arọ nke 22.8% na 24.2%, n'otu n'otu. N'ọkwa ọzọ nke abụọ kpuru ìsì abụọ, randomized, ebe a na-achịkwa ebebo, ndị ọrịa nọ n'ìgwè dose dị iche iche nwetara ogo dị iche iche nke ịdị arọ na izu 24 na izu 48. Otu 12mg nwetara mbelata ibu nke 24.2% na izu 48, ebe ndị otu placebo hụrụ mbelata -2.1%. Retatrutide na-ebelata ibu ahụ nke ọma na ndị ọrịa buru ibu, na-enye ngwá ọrụ ọhụrụ dị ike maka ọgwụgwọ oke ibu. Usoro ọgwụgwọ Retatrutide maka oke ibu ọ bụghị naanị na-ebelata ibu ahụ kamakwa ọ nwekwara ike imeziwanye nsogbu ahụike ndị ọzọ metụtara oke ibu, dị ka ibelata nrụgide nkwonkwo na iwepụ ihe mgbaàmà nke ọrịa nkwonkwo metụtara oke ibu site na nkwụsị ibu; Mbelata ibu ahụ nwekwara ike inye aka melite nsogbu ndị metụtara oke ibu dị ka apnea ụra ^[3,6].

Usoro ọgwụgwọ metabolism nke ụdị 2: 

Metabolism ụdị 2 bụ ọrịa metabolic na-adịghị ala ala nke e ji nguzogide insulin na ụkọ insulin ezughi oke. Retatrutide nwere uru ngwa ngwa na ọgwụgwọ nke ụdị 2 metabolism. Ọ na-akpali mmepụta insulin site na ịgbalite onye na-anabata GLP-1, na-eme ka nguzogide insulin dịkwuo mma, na-ebelata ọkwa glucose ọbara. Mmetụta na-ebelata ibu ya na-enyekwa aka melite ọnọdụ nke ụdị 2 nke ndị ọrịa na-arịa ọrịa metabolism, n'ihi na oke ibu bụ ihe dị mkpa dị ize ndụ maka ụdị 2 metabolism, na ọnwụ dị arọ nwere ike ime ka mmetụta insulin dịkwuo elu, na-enye aka n'ihu n'ịchịkwa glucose ọbara. N'ime ọmụmụ ihe metụtara ndị ọrịa nwere ụdị metabolism nke 2, Retatrutide butere oke ibu na mbelata ọkwa haemoglobin A1c (HbA1c), yana HbA1c na-agbada site na 1.64% ma e jiri ya tụnyere placebo. Nke a na-egosi na Retatrutide abụghị naanị na-achịkwa ọkwa glucose ọbara n'ụzọ dị irè kamakwa ọ na-eme ka ọnọdụ ndị ọrịa nwere ụdị 2 metabolism dịkwuo mma site n'ọtụtụ usoro, gụnyere oke ibu, si otú ahụ na-eme ka ndụ ha dịkwuo mma ^[6]..

Ọgwụgwọ ọrịa imeju na-adịghị egbu egbu (NAFLD): 

NAFLD bụ mmerụ ahụ nke imeju na-akpata nrụgide metabolic jikọtara ya na nguzogide insulin na ike mkpụrụ ndụ ihe nketa, na-agụnye ọnọdụ dị iche iche gụnyere imeju abụba na-abụghị mmanya na-aba n'anya, steatohepatitis na-abụghị mmanya na-aba n'anya, na cirrhosis metụtara ya. Retatrutide na-egosi ikike na-ekwe nkwa na ọgwụgwọ NAFLD. Na a randomized, okpukpu abụọ-ìsì, placebo-achịkwa ikpe metụtara ndị sonyere na metabolic dysfunction-metụtara abụba imeju ọrịa na imeju abụba ọdịnaya ≥10%, na 24 izu, pụtara ikwu mgbanwe n'ime imeju abụba ọdịnaya si baseline dị nnọọ iche n'ofe Retatrutide dose otu: -81.4% na 8mg otu, -82.4% n'ime otu placebo, na +10 mg. Nke a na-egosi na Retatrutide nwere ike belata ọdịnaya abụba imeju nke ọma, nke dị oke mkpa maka imezi usoro imeju nke ndị ọrịa NAFLD. Ọ na-ekwe nkwa dị ka nhọrọ ọgwụgwọ ọhụrụ maka NAFLD, nwere ike ibelata ọganihu ọrịa yana ibelata ihe ize ndụ nke nsogbu siri ike dị ka cirrhosis ^[3].

Mmechi

Retatrutide na-egosi ikike na-ekwe nkwa imeziwanye ọnọdụ ọrịa imeju nke ndị ọrịa NAFLD, na-eme site na ọtụtụ usoro gụnyere ịhazi metabolism ike, melite nguzogide insulin, mmetụta mgbochi mkpali, na mezie metabolism lipid.

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

Rosenstock, J bụ ọkà mmụta pụtara ìhè nke ọrụ ya nwere njikọ chiri anya na ọtụtụ ụlọ ọrụ ama ama, gụnyere Mahadum Texas Southwestern Medical Center, Mahadum Texas Dallas, na Canadian VIGOR Center. Nnyocha ya gbasara ọtụtụ ngalaba dị ka Endocrinology & Diabetes, General & Internal Medicine, Cardiovascular System & Cardiology, Pharmacology & Pharmacy, na Research & Experimental Medicine. Ntụnye dị ịrịba ama o nyere ndị obodo agụmakwụkwọ emeela ka ọ nweta nkwanye ùgwù zuru oke, dị ka egosipụtara site na nhọpụta ya ugboro ugboro dị ka onye nyocha nke ọma na ngalaba nke Clinical Medicine site na 2017 ruo 2024, na-egosipụta ọkwa ya dị ịrịba ama na mmetụta dị ukwuu na nyocha ahụike ụlọ ọgwụ. A na-edepụta Rosenstock J n'akwụkwọ ntụaka [4].

▎ Okwu ndị dị mkpa

[1] Brzozowska P, Frańczuk A, Nowińska B, et al. Retatrutide - mgbanwe mgbanwe na-adịbeghị anya mepụtara GLP agonist - nyocha akwụkwọ[J]. Ogo na egwuregwu, 2024.DOI:10.12775/qs.2024.15.52125.

[2] Doggrell SA Retatrutide na-egosi nkwa na oke ibu (na ụdị 2 metabolism) [J]. Echiche ndị ọkachamara na ọgwụ nyocha, 2023,32 (11): 997-1001.DOI: 10.1080/13543784.2023.2283020.

[3] Sanyal AJ, Kaplan LM, Frias JP, et al. agonist Triple hormone receptor agonist Retatrutide maka ọrịa ọrịa imeju steatotic metụtara metabolic dysfunction: usoro 2a na-enweghị usoro [J]. Ọgwụ okike, 2024,30:2037-2048.DOI:10.1038/s41591-024-03018-2.

[4] Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, GIP, GLP-1 na glucagon agonist receptor, maka ndị nwere ụdị 2 metabolism: a randomized, double-kpuru, placebo na arụ ọrụ-achịkwa, otu-otu, usoro 2 ikpe emere na USA[J]. Lancet, 2023,402 (10401):529-544.DOI:10.1016/S0140-6736(23)01053-X.

[5] Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide maka oke ibu - Ọnwụnwa nke 2[J]. Akwụkwọ akụkọ ọgwụ New England, 2023,389 (6): 514-526.DOI: 10.1056/NEJMoa2301972.

[6] Lopez DC, Pajimna JT, Milan MD, et al. 7792 arụmọrụ nke Retatrutide maka Mbelata ibu na Mmetụta Cardiometabolic Ya n'etiti Ndị okenye: Nyochaa Usoro na Meta-Analysis[J]. Akwụkwọ akụkọ nke Endocrine Society, 2024,8 (1): 163-749.DOI: 10.1210/jendso/bvae163.749.

[7] Nicholls S, Pirro V, Lin Y, et al. agonist Triple-hormone receptor agonist Retatrutide na-emeziwanye profaịlụ lipoprotein na apolipoprotein na ndị sonyere na oke ibu ma ọ bụ oke ibu[J]. Akwụkwọ akụkọ obi European, 2024,45 (1): 666-1501.DOI: 10.1093/eurheartj/ehae666.1501.

[8] Katsi V, Koutsopoulos G, Fragoulis C, et al. Retatrutide—Onye na-agbanwe egwuregwu na oke ibu ọgwụ: Biomolecules[Z]. 2025: 15.DOI: 10.3390/biom15060796.

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) akwadobeghị 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.