Retatrutid 10 mg

▎ Ọdịdị Retatrutid

▎ Nnyocha Retatrutid

Kedu ihe ndabere nyocha nke Retatrutid?

Oke ibu bụ otu n'ime nsogbu ahụike ọha na eze taa. Ibu oke ibu nwere ike ibute nsogbu ahụike dị iche iche, dị ka ụdị ọrịa shuga 2, ọrịa obi, ọbara mgbali elu, dyslipidemia, na ọrịa imeju na-adịghị egbu egbu. Site na mmụba na-aga n'ihu na mmụba nke oke ibu, a na-enwewanye ọchịchọ maka ọgwụgwọ ọhụrụ nke nwere ike ijikwa oke ahụ nke ọma ma melite ọnọdụ ahụike ^[1] . Ọ bụ ezie na mgbanwe ndụ, dị ka ịba ụba nke mmega ahụ na ibelata nri oriri, bụ ụzọ ndị bụ isi maka njikwa ibu, ogologo oge na-edozi oke ibu na-anọgide na-esiri ọtụtụ ndị okenye emetụta. Retatrutid bụ agonist atọ na-anabata akwụkwọ akụkọ nke na-arụ ọrụ na glucagon-dị ka peptide-1 receptor (GLP-1R), glucose-based insulinotropic polypeptide receptor (GIPR), na glucagon receptor (GCGR). Nke a multi-receptor usoro nke edinam na-enye ya pụrụ iche uru na arọ ọnwụ. E jiri ya tụnyere ọgwụ na-ebelata ibu nke na-arụ ọrụ n'otu onye na-anabata ya, Retatrutid nwere ike ịhazi usoro metabolic nke anụ ahụ n'ụzọ zuru ezu ^[1] . Retatrutid na-enweta oke ibu site na ịhazi ọtụtụ ndị na-anabata homonụ. Ọ bụghị naanị na ọ nwere mmetụta dị oke ibu dị arọ kamakwa ọ nwere mmetụta dị nro dị nro nke eriri afọ. Na mgbakwunye, atụnyere ọgwụ ndị ọzọ na-ebelata ibu arọ, Retatrutid, dị ka onye na-anabata agonist ugboro atọ, nwere mmetụta mbelata ibu dị ike karị yana ọnụ ọgụgụ dị ukwuu nke ndị mmadụ.

Kedu ihe bụ usoro Retatrutid?

Usoro nke Retatrutid na-esite na mmetụta ya na-akpata na ọtụtụ ndị na-anabata ya. Nke mbụ, mmetụta ya na-egbu egbu na glucagon-dị ka peptide-1 receptor (GLP-1R) na-abawanye mmepụta insulin, na-egbochi secretion glucagon, na-ebelata ọkwa glucose ọbara, ma n'otu oge ahụ na-egbu oge ịwụsa afọ, na-abawanye satiety, ma na-ebelata oriri ^[2] . Nke abuo, mmetụta agonist ya na onye na-anabata insulinotropic polypeptide (GIPR) na-adabere na glucose nwere ike ịkwalite mmepụta insulin, mee ka ojiji glucose dịkwuo elu, ma nwee mmetụta na metabolism abụba, na-egbochi lipolysis na ịkwalite njikọ abụba ^[2] . Ọzọkwa, ọ bụ ezie na mmetụta agonistic nke Retatrutid na onye na-anabata glucagon (GCGR) na-akwalitekarị glycogenolysis na gluconeogenesis na imeju, na-abawanye ọkwa glucose ọbara, n'okpuru ọrụ Retatrutid, mmetụta a nke ịba ụba glucose ọbara na-ebelata site na mmetụta nke ndị na-anabata ndị ọzọ abụọ. N'otu oge ahụ, ọ na-akwalite lipolysis ma na-ebelata mkpokọta abụba ^[2] . Ụdị omume a nwere ọtụtụ ebumnuche nwere ike ịdị irè karịa n'ịgwọ oke ibu karịa otu agonists nnabata.

Site n'otu oge na-eme ka ndị nnata atọ a rụọ ọrụ, Retatrutid nwere ike ịmepụta mmetụta dị iche iche nke usoro metabolic ma mepụta mmetụta ọgwụgwọ na oke ibu na ọrịa ndị metụtara ya. N'ihe banyere ịhazi ọkwa glucose ọbara, n'ihi ịgbalite GLP-1R na GIPR na-akwalite mmepụta insulin na igbochi secretion glucagon, yana ịgbalite GCGR site na mmetụta nke ndị nnabata abụọ ndị ọzọ, Retatrutid nwere ike ịhazi ọkwa glucose ọbara nke ọma, nke dị oke mkpa maka ọgwụgwọ ụdị ọrịa shuga 2 ^{, 1} . N'ihe banyere ibelata mkpokọta abụba, ịgbalite GCGR na-akwalite lipolysis ma belata mkpokọta abụba. N'otu oge ahụ, ịgbalite GLP-1R na-abawanye satiety ma belata oriri nri, na-ebelata njikọ abụba ^{[1, 2]} . Na mgbakwunye, Retatrutid nwekwara mmetụta bara uru na ọrịa imeju na-adịghị egbu egbu. Ọ nwere ike ibelata abụba dị n'imeju ma melite ọrụ imeju. Nnwale a na-achịkwaghị achịkwa, nke kpuru ìsì abụọ, gosipụtara na nkezi mgbanwe mgbanwe nke abụba imeju na otu ọgwụgwọ Retatrutid na izu 24 dị obere karịa nke ahụ na placebo otu ^[3].

HbA1c, arọ ahụ, ọbara mgbali elu, na lipids Data bụ ụzọ opekata mpe-squares (ya na mpe mpe mpe mpe mpe mpe mpe mpe mpe mpe mpe mpe mperi na-egosi SE) site na nhazi nyocha nrụpụta ọrụ, belụsọ na amataghi ya.

Isi mmalite: PubMed ^[4]

Kedu ka Retatrutid si ahazi glucose metabolism mgbe ọ gbasịrị ndị nnabata atọ ahụ?

Retatrutid na-achịkwa glucose ọbara site na usoro dị iche iche, gụnyere ịgbalite GLP-1 na GIP ndị na-anabata ya, na-akpali mmepụta insulin, na-egbochi secretion glucagon, na-egbu oge ịgbasa gastric, na-achịkwa metabolism abụba, na ibelata ọkwa ANGPTL3/8. N'ihe banyere usoro glucose ọbara, Retatrutid na-arụ ọrụ na GLP-1 na ndị na-anabata GIP, na-akwalite mmetụta nke mkpụrụ ndụ β pancreatic na glucose, na-emepụta ma na-ahapụ insulin, wee kwalite nnabata na ojiji nke glucose site na anụ ahụ, na-enweta mmetụta nke ibelata glucose ọbara ^{[4, 5]} . (HbA1c), nke na-erite uru nke ukwuu site na ọrụ ya na-akpali mmepụta insulin (Rosenstock J, 2023). N'otu oge ahụ, ịgbalite GLP-1 nnabata nwere ike igbochi nzuzo nke glucagon site na mkpụrụ ndụ α pancreatic, na-egbochi glucose ọbara ka ọ dị elu. Na nyocha ụlọ ọgwụ, a chọpụtala na ọkwa glucagon nke ndị ọrịa na-eji Retatrutid ebelatala, nke na-enyere aka ịnọgide na-enwe nkwụsi ike nke glucose ọbara ^{[4, 5]} . Ịrụ ọrụ GLP-1 na GIP ndị na-anabata ya nwekwara ike igbu oge ọnụego nke mkpofu afọ, belata mgbaze na nnabata nri, ma belata ịrị elu nke glucose ọbara mgbe nri gasịrị. Nnyocha egosiwo na oge mkpofu afọ nke ndị ọrịa a na-agwọ Retatrutid na-agbatịkwu ogologo oge mgbe ha risịrị nri, si otú a na-ebelata uru kachasị elu nke glucose ọbara postprandial ^[4]..

Usoro nke metabolism abụba site na Retatrutid na-emetụtakwa metabolism glucose na-apụtaghị ìhè. Dịka ọmụmaatụ, na ọmụmụ banyere ndị ọrịa buru ibu, a chọpụtala na Retatrutid nwere ike ibelata ọkwa nke triglycerides (TG), lipoprotein dị ala (LDL), na oke-njupụta lipoprotein (VLDL) cholesterol ^{[2, 6]} . Ọganihu a na metabolism lipid nwere ike jikọta ya na mmụba nke mmetụta insulin, si otú a na-enye aka na njikwa glucose ọbara. Kpọmkwem, mgbe ọgwụgwọ Retatrutid gasịrị, plasma 3-hydroxybutyric acid (3-HB) na-abawanye, yana mmụba nke 3-hydroxybutyrylcarnitine (C ₄OH), oke acetylcarnitine na carnitine efu (C ₂/ C ₀), na acylcarnitine na-ajụ ọkara, na-egosi mmụba lipolysis na anụ ahụ na-abawanye ụba na abụba oxidation.

Retatrutid nwekwara ike ibelata mkpokọta dihydroceramides (DhCers), mgbanwe a na-ejikọta ya na mmụba insulin ka mma, belata steatosis hepatic, na mbufụt sistemu ⁶ [ ^] . ANGPTL3/8 bụ onye na-egbochi mgbasa nke lipoprotein lipase (LPL) kachasị dị irè, yana ọkwa ọbara ya na-emetụta TG na cholesterol lipoprotein dị ala (LDL-C). Retatrutid na-ebelata ọkwa ANGPTL3/8, nke nwere ike ịhazi glucose metabolism site na ibelata lipoproteins bara ụba nke triglyceride ^. .

N'akụkụ dị aṅaa ka Retatrutid na-egosi mmetụta ya?

Mmetụta mbelata ibu dị mkpa: 

Retatrutid egosila mmetụta mbelata ibu dị ukwuu n'ọtụtụ ule ụlọ ọgwụ. Dịka ọmụmaatụ, na nyocha ụlọ ọgwụ metụtara ndị okenye 338 ^[2] , ndị ọrịa na-agwọ ọrịa dị iche iche nke Retatrutid nwere oke ibu dị arọ na izu 48. N'ime ha, ndị ọrịa nọ na 12mg dose otu nwere oke ibu nke 24.2%, na ọnụ ọgụgụ dị elu nke ndị ọrịa nwetara ọnwụ dị arọ na ogo dịgasị iche iche. Dịka ọmụmaatụ, n'etiti ndị ọrịa na-anata 4mg, 8mg, na 12mg doses, 92%, 100%, na 100% nke ndị ọrịa tụfuru 5% ma ọ bụ karịa nke ahụ ha, n'otu n'otu. N'ọmụmụ ihe ọzọ ^[8] , ule abụọ a na-achịkwa nke na-agụnye ndị ọrịa 353 ụdị ọrịa shuga 2 gosiri na e jiri ya tụnyere placebo, Retatrutid nwere ike ibelata ịdị arọ nke ndị ọrịa site na 11.89kg ma belata haemoglobin glycated (HbA1C). Na mgbakwunye, na nnwale nke ndị okenye buru ibu na-abụghị ndị ọrịa mamịrị, Retatrutid kpatara mbelata ibu nke 24.2% na ndị ọrịa, na 83% nke ndị ọrịa tụfuru 15% ma ọ bụ karịa nke ahụ ha na izu 48. Nsonaazụ ndị a na-egosi na Retatrutid nwere ikike dị ukwuu na mbelata ibu.

Ọgwụgwọ nke ụdị ọrịa shuga 2 : 

Retatrutid na-egosikwa ụfọdụ ike na ọgwụgwọ ụdị ọrịa shuga 2. N'ime ule ụfọdụ ụlọ ọgwụ, Retatrutid egosila mbelata nke haemoglobin glycated (HbA1c) yana mbelata ibu nke dabere na dose. Dịka ọmụmaatụ, n'otu nnyocha, na ụdị ọrịa shuga 2, Retatrutid gosipụtara mmetụta nchịkwa glucose ọbara dị ịrịba ama, na-ebelata hemoglobin glycated site na 1.64% ma e jiri ya tụnyere placebo ^{[4, 8]} . Tụkwasị na nke ahụ, n'ime usoro 2 nke a na-ahụghị anya, nke kpuru ìsì, na-arụ ọrụ na-arụ ọrụ na-arụ ọrụ na-arụ ọrụ na-arụkọ ọrụ ọnụ, ụdị anụmanụ ndị nwere ụdị ọrịa shuga 2 gosipụtara mbelata dị ukwuu na ọkwa hemoglobin glycated na nkwụsị nke na-adabere na dose mgbe ọ natara ọgwụgwọ Retatrutid ^[4] . Enwere ike ịsị na nke a bụ nsonaazụ zuru oke nke ọgwụ na GLP-1, GCGR, na GIPR, nke na-eme ka metabolism glucose dịkwuo elu na nguzozi ike.

Mmelite nke ihe ize ndụ nke obi: 

Retatrutid nwere ike ọ bụghị naanị ibelata ibu ahụ kamakwa melite ihe ize ndụ nke obi, dị ka profaịlụ ọbara lipid na ọkwa hemoglobin glycated. Nke a na-egosi njikọ chiri anya pathophysiological n'etiti oke ibu na ọrịa obi, na Retatrutid nwere ike melite ahụike obi nke ndị ọrịa buru ibu site na ọtụtụ ụzọ. Dịka ọmụmaatụ, ibelata ọkwa na-abụghị HDL-C, apoB, na LDLP nwere ike ibelata ihe ize ndụ nke atherosclerosis; Mbelata ọkwa hemoglobin glycated nwere ike imezi njikwa glucose ọbara n'ime ndị ọrịa shuga, si otú ahụ belata ihe ize ndụ nke nsogbu obi obi ^[8-10]. .

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

Retatrutid bụ peptide nke na-anabata glucagon receptor (GCGR), insulinotropic polypeptide receptor (GIPR) dabere na glucose na onye nata glucagon dị ka peptide-1 (GLP-1R). Nnyocha egosiwo na Retatrutid nwere ikike n'ịgwọ ọrịa imeju na-adịghị egbu egbu. N'ime otu ọmụmụ, a na-eme nchọpụta a na-achịkwaghị achịkwa, nke kpuru ìsì abụọ, ebe a na-achịkwa placebo na-adịgide adịgide izu 48 na ndị na-eso ya nwere ọrịa imeju abụba na-emetụta metabolic dysfunction na ọdịnaya abụba imeju nke ≥10%. Nsonaazụ gosiri na n'ime izu 24, nkezi mgbanwe na abụba imeju na-adabere na ntọala nke ndị na-eso ụzọ na-emeso ọgwụ dị iche iche nke Retatrutid (1mg, 4mg, 8mg, na 12mg) bụ -42.9%, -57.0%, -81.4%, na -82.4%, n'otu n'otu, ebe nke ahụ nọ na placebo otu bụ + 3.3 ^% . Nke a na-egosi na Retatrutid nwere ike inwe mmetụta ọgwụgwọ dị ukwuu na ọrịa imeju na-adịghị egbu egbu.

Na mmechi, dị ka akwụkwọ akụkọ atọ agonist receptor, Retatrutid na-egosi nnukwu ikike na ọgwụgwọ oke ibu na ọrịa ndị metụtara ya. Ọ nwere ike ịgbalite onye na-anabata glucagon, onye na-anabata insulinotropic polypeptide na-adabere na glucose, yana onye na-anabata glucagon-dị ka peptide-1, na-achịkwa metabolism nke anụ ahụ site n'ọtụtụ akụkụ, na-eme ka njikwa glucose ọbara dị mma, na-ebelata ibu ahụ, na-ahazi metabolism lipid. Mpụta nke Retatrutid na-eweta nhọrọ ọgwụgwọ ọhụrụ maka ndị ọrịa nwere oke ibu, ụdị ọrịa shuga 2, na ọrịa ndị ọzọ. A na-atụ anya na ọ ga-emebi site na njedebe nke ọgwụ agonist otu onye na-anabata ihe, na-enye ngwá agha dị ike karị maka idozi nsogbu ndị na-arịwanye elu nke oke ibu na ọrịa metabolic, na-akwalite ọganihu n'ihu nke ngalaba ahụike metụtara ya, melite ogo ndụ nke ndị ọrịa, ma belata ibu ọrụ ahụike ọha na eze.

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 nwere mmetụta dị ukwuu na ngalaba ahụike, na-arụkọ ọrụ ọnụ na ụlọ ọrụ dịka Mahadum Texas Southwestern Medical Center na Mahadum Texas Dallas. Ọ na-eduzi nyocha na ụlọ ọrụ dịka Canadian VIGOR Center na Veloc Clin Res Ctr Med City. Nchoputa ya gbasara endocrinology na metabolism, sistemu obi obi na akwara obi, pharmacology, na nnwale nnwale, na-elekwasị anya na ọrịa shuga, oke ibu, na ọgwụgwọ ndị metụtara ya na mmepe ọgwụ. J Rosenstock enwetawo ihe ịga nke ọma dị ịrịba ama na nkà mmụta ọgwụ, n'ịbụ onye a na-akpọ onye nyocha nke ukwuu site na 2017 ruo 2024. Nke a na-egosipụta mmetụta dị elu na nkwanye ùgwù sara mbara nke ọrụ ya. Site na mmekorita ya na ụlọ ọrụ nyocha dị iche iche, ọ tụgharịrị nke ọma nchọpụta nchọpụta bụ isi n'ime ngwa ụlọ ọgwụ, na-erite uru ndị ọrịa nwere ọrịa metabolic na ọrịa obi na ịkwalite sayensị ahụike. A na-edepụta Rosenstock J n'akwụkwọ ntụaka [4].

▎ Okwu ndị dị mkpa

[1] Kaur M, Misra S. Ntụleghachi nke nyocha ọgwụ retatrutide, 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.

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

[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 (7): 2037-2048.DOI:10.1038/s41591-024-03018-2.

[4] Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutid, GIP, GLP-1 na glucagon agonist receptor, maka ndị nwere ụdị ọrịa shuga 2: ihe na-adịghị ahụkebe, ndị ìsì abụọ, placebo na ndị na-arụ ọrụ na-achịkwa, otu-otu, nnwale 2 nke emere na USA[J]. Lancet, 2023,402 (10401):529-544.DOI:10.1016/S0140-6736(23)01053-X.

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

[6] Pirro V, Pearson MJ, Lin Y, et al. Mmetụta nke Triple-Hormone Nnabata Agonist Retatrutid na Profaịlụ Lipid na Ndị sonyere na oke ibu[J]. Ọrịa shuga, 2024,73.DOI:10.2337/db24-117-OR.

[7] Wen Y, Lemen D, Chen Y, et al. Enwere ike ịkọwa mbelata lipoproteins bara ụba nke triglyceride na retatrutide na ụdị ọrịa shuga 2 site na mbelata otu oge na ọkwa ANGPTL3/8[J]. Akwụkwọ akụkọ obi European, 2024,45.DOI:10.1093/eurheartj/ehae666.2862.

[8] 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 (1): 163-749.DOI: 10.1210/jendso/bvae163.749.

[9] Nicholls S, Pirro V, Lin Y, et al. Agonist retatrutide na-anabata homonụ atọ na-eme ka profaịlụ lipoprotein na apolipoprotein dịkwuo mma na ndị sonyere nwere oke ibu ma ọ bụ oke ibu[J]. Akwụkwọ akụkọ obi European, 2024,45.DOI:10.1093/eurheartj/ehae666.1501.

[10] Ray A. Retatrutid: agonist atọ incretin receptor agonist maka njikwa oke ibu [J]. Echiche ndị ọkachamara na ọgwụ nyocha, 2023,32 (11): 1003-1008.DOI: 10.1080/13543784.2023.2276754.

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.