1kits (Ebipipa 10) .
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▎ Okukubaganya ebirowoozo ku Retatrutid
Retatrutid ddagala lya peptide eripya. Nga agonist ya triple receptor agonist, ekola ku glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ne glucagon receptors omulundi gumu. Kiyamba abantu ssekinnoomu okugejja nga kitereeza mu bujjuvu okwagala okulya, okwongera okukkuta, okuziyiza enjala n’okwongera ku nsaasaanya y’amaanyi.
Okugatta ku ekyo, Retatrutid era esobola okulongoosa ebiraga akabi k’omutima n’enkyukakyuka mu mubiri, gamba nga puleesa, glycated hemoglobin, glucose mu musaayi mu kisiibo, insulin, kolesterol yenna, low-density lipoprotein cholesterol, ne triglycerides. Era kikola bulungi ku balwadde abalina obulwadde bw’ekibumba obw’amasavu agatali ga mwenge, ekisobozesa amasavu mu kibumba g’abasinga obungi abeetabye mu kugezesebwa okudda mu mbeera eya bulijjo.
Bw’ogeraageranya ne agonists emu oba bbiri, Retatrutid etereeza glucose mu musaayi, obuzito bw’omubiri n’ebirala okuva mu bipimo ebingi ng’ekola omulundi gumu ebitundu ebisatu ebikwata GLP-1, GIP, ne glucagon (GCG). Mu ndowooza, esobola okulongoosa mu bujjuvu obuzibu mu nkyukakyuka y’emmere era erina ebirungi eby’enjawulo mu bintu ng’okugejja, okukendeeza ku bulwadde bw’ekibumba, n’okuzza emiwendo gya glucose mu musaayi mu mbeera eya bulijjo.
Ekikolwa ky’okukwatagana kw’ebirungo ebingi ebya Retatrutid kigifuula ennungi okusinga eddagala erikwata GLP-1 oba dual receptor agonists eriwo mu kulungamya enkyukakyuka mu mubiri n’okufuga obuzito bw’omubiri, okuwa obujjanjabi obupya eri abalwadde abagejjulukuka ne ssukaali ow’ekika eky’okubiri.
▎ Okunoonyereza ku Retatrutid
Retatrutid yakola mu kunoonyereza kuliwa?
Omugejjo gufuuse ekimu ku bisinga okusoomoozebwa mu bulamu bw’abantu mu bantu ab’omulembe guno. Kiyinza okuvaako ebizibu by’obulamu bingi nga sukaali ow’ekika eky’okubiri, endwadde z’emisuwa, puleesa, okukendeeza ku masavu, n’obulwadde bw’ekibumba obutaliimu masavu. Olw’okweyongera kw’abagejjulukuka buli kiseera, waliwo obwetaavu obweyongera obw’amangu obw’obujjanjabi obupya obusobola okuddukanya obulungi obuzito bw’omubiri n’okulongoosa embeera z’obulamu [1] . Newankubadde nga okuyingira mu bulamu, gamba ng‟okwongera okukola emirimu gy‟omubiri n‟okufuga emmere, bye bipimo ebikulu eby‟okuziyiza omugejjo, kizibu nnyo eri abalwadde bangi abakulu abagejjulukuka okukuuma okugejja okumala ebbanga eddene.
Retatrutid, nga ekirungo ekipya ekiziyiza okukwata ebitundu bisatu, asobola okukola ku kirungo kya peptide-1 ekiringa glucagon (
GLP-1R), ekirungo kya insulinotropic polypeptide ekisinziira ku glucose (GIPR), n’ekirungo kya glucagon (GCGR). Enkola eno ey’okukola ey’ebifo ebingi egiwa enkizo ennene mu kisaawe ky’okugejja. Bw’ogeraageranya n’eddagala erikendeeza ku buzito erikola ku kifo kimu kyokka, Retatrutid esobola okulung’amya mu bujjuvu enkola z’omubiri mu mubiri [1] . Retatrutid etuuka ku kugejja ng’etereeza ebifo ebikwata obusimu ebingi, tekoma ku kulaga bulungibwansi bwa kitalo naye era n’ebizibu ebitono ennyo mu lubuto n’ekyenda. Okugatta ku ekyo, nga triple receptor agonist, Retatrutid erina amaanyi amangi agakola ku kugejja n’omuwendo omunene ogw’abantu abakozesebwa bw’ogeraageranya n’eddagala eddala eppya erigejja.
Retatrutid kye ki?
Retatrutid ye nkola empya ekola okumala ebbanga eddene nga glucagon-like peptide-1 (GLP-1) receptor agonist. Kikyusibwa era ne kirongooseddwa okusinziira ku nsengeka ya GLP-1 ey’obutonde, era kisobola okwesiba mu ngeri ey’enjawulo n’okukola ku kikwata GLP-1, okukola emirimu gy’omubiri okufaananako n’egya GLP-1 ey’obutonde, gamba ng’okutumbula okufulumya insulini, okuziyiza okufulumya glucagon, okulwawo okufulumya amazzi mu lubuto, okukendeeza ku njagala y’okulya, n’ebirala Kirina essuubi erigazi okukozesebwa mu kujjanjaba obulwadde bwa sukaali n’okuddukanya obuzito.
Enkola ya Retatrutid ekola ki?
Enkola y’okukola kwa Retatrutid eva ku bikolwa byayo eby’ekika kya agonistic ku bikwata ebingi. Ekisooka, agonistic effect yaayo ku glucagon-like peptide-1 receptor (GLP-1R) esobola okwongera ku kufulumya insulini, okuziyiza okufulumya glucagon, okukendeeza ku glucose mu musaayi, ate mu kiseera kye kimu okulwawo okufulumya amazzi mu lubuto, okwongera okukkuta, n’okukendeeza ku mmere gy’olya [2] . Ekirala, agonistic effect yaayo ku glucose-dependent insulinotropic polypeptide receptor (GIPR) esobola okutumbula okufulumya insulin, okutumbula enkozesa ya glucose, n’okukosa metabolism y’amasavu, okuziyiza lipolysis n’okutumbula okukola amasavu [2] . Ekirala, agonistic effect ya Retatrutid ku glucagon receptor (GCGR) etera okutumbula glycogenolysis ne gluconeogenesis mu kibumba, okwongera ku glucose mu musaayi. Naye, wansi w’ekikolwa kya Retatrutid, kino ekikolwa eky’okusitula glucose kikyusibwakyusibwa ebikolwa by’ebikwata ebirala ebibiri, ate nga kitumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu [2] . Enkola eno ey’okukola erimu ebigendererwa ebingi eyinza okuba ennungi mu kujjanjaba omugejjo okusinga eddagala eriziyiza obuwuka obuyitibwa single receptor agonists.
Nga ekola mu kiseera kye kimu ebikwata bino ebisatu, Retatrutid esobola okukola ebikolwa eby’enjawulo ebifuga enkyukakyuka mu mubiri n’okukola ebikolwa eby’obujjanjabi ku mugejjo n’endwadde ezikwatagana nabyo. Mu nsonga y’okulungamya emiwendo gya glucose mu musaayi, okuva okukola kwa GLP-1R ne GIPR bwe kutumbula okufulumya insulini n’okuziyiza okufulumya glucagon, era okukola kwa GCGR kukyusibwakyusibwa olw’ebikolwa by’ebikwata ebirala ebibiri, Retatrutid esobola bulungi okutereeza emiwendo gya glucose mu musaayi, ekintu eky’amakulu mangi mu kujjanjaba ssukaali ow’ekika eky’okubiri [1, 2] . Mu nsonga y’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, okukola kwa GCGR kutumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, ate okukola kwa GLP-1R kwongera okukkuta n’okukendeeza ku mmere, okwongera okukendeeza ku kusengejja amasavu [1] . Okugatta ku ekyo, Retatrutid era erina ekikolwa ekirongoosa ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Kisobola okukendeeza amasavu mu kibumba n’okulongoosa enkola y’ekibumba.


HbA1c, obuzito bw’omubiri, puleesa, n’amasavu Data zibeera least-squares means (nga zirina error bars eziraga SEs) okuva mu efficacy analysis set, okuggyako nga kiragiddwa bulala.
Ensibuko:PubMed [4] .
Mu bintu ki Retatrutid mw’alaga ebivaamu?
Retatrutid eraga ebikosa ebinene mu bintu ebingi
Ekinene ekiva mu kugejja: Retatrutid eraga ebikolwa ebinene mu kugejja mu kugezesebwa okw’obujjanjabi okungi. Okugeza, mu kunoonyereza okwakolebwa mu bujjanjabi okwali kuzingiramu abantu abakulu 338 (Jastreboff AMM, 2023), abalwadde abajjanjabwa ne dose ez’enjawulo eza Retatrutid baafuna okugejja okw’amaanyi ku wiiki 48. Mu bano, abalwadde mu kibinja kya ddoozi ya 12mg baafiirwa ebitundu 24.2% ku buzito bw’omubiri gwabwe, era ekitundu ekinene eky’abalwadde baatuuka ku kugejja ku diguli ez’enjawulo. Okugeza, mu balwadde abafuna dose ya 4mg, 8mg, ne 12mg, 92%, 100%, ne 100% ku balwadde, okusinziira ku, baakendeeza ku buzito bw’omubiri gwabwe ebitundu 5% oba okusingawo. Mu kunoonyereza okulala [3] , okugezesebwa okubiri okwakolebwa mu ngeri ey’ekifuulannenge okwali kuzingiramu abalwadde 353 abalina ssukaali ow’ekika eky’okubiri kwalaga nti bw’ogeraageranya n’eddagala erya placebo, Retatrutid esobola okukendeeza ennyo ku buzito bw’omubiri gw’abalwadde 11.89kg, era n’okukendeeza ku glycated hemoglobin (HbA1C). Okugatta ku ekyo, mu kugezesebwa kw’abalwadde abakulu abagejjulukuka nga tebalina sukaali, Retatrutid yaleeta okugejja ebitundu 24.2% mu balwadde, ate abalwadde 83% ne bakendeeza ku buzito bw’omubiri gwabwe ebitundu 15% oba okusingawo ku wiiki 48. Ebivudde mu kunoonyereza kuno biraga nti Retatrutid erina obusobozi bungi mu kugejja.
Obujjanjabi bwa sukaali ow’ekika eky’okubiri: Retatrutid era eraga obusobozi obumu mu kujjanjaba obulwadde bwa sukaali obw’ekika eky’okubiri. Mu kugezesebwa okumu, Retatrutid eraga okukendeera mu glycated hemoglobin (HbA1c) n’okugejja okusinziira ku ddoozi. Okugeza, mu kunoonyereza okumu, mu balwadde abalina ssukaali ow’ekika eky’okubiri, Retatrutid yalaga nti ekola kinene mu kufuga glucose mu musaayi. Bw’ogeraageranya n’eddagala erya placebo, glycated hemoglobin yakendeera ebitundu 1.64% [3] . Okugatta ku ekyo, mu kugezesebwa okwa randomized, double-blind, placebo ne active-controlled parallel-group phase 2 trial, ebisolo models ebirina type 2 diabetes mellitus, oluvannyuma lw’okufuna obujjanjabi Retatrutid, yalaga okukendeera okw’amaanyi mu glycated hemoglobin levels, era obuzito bw’omubiri gwabwe nagwo bwakendeera mu ngeri eyeesigama ku dose [4] . Kino kiyinza okuva ku bikolwa byonna eby’eddagala lino ku GLP-1, GCGR, ne GIPR, ebirongoosa enkyukakyuka ya glucose n’okutebenkeza amaanyi.
Okulongoosa ensonga z’obulabe eri emisuwa: Retatrutid tesobola kukendeeza ku buzito bw’omubiri gwokka wabula n’okulongoosa ensonga z’obulabe eri emisuwa, gamba nga serum lipid profile ne glycated hemoglobin levels. Kino kiraga akakwate ak’okumpi mu pathophysiological wakati w’omugejjo n’endwadde z’emisuwa, era Retatrutid eyinza okulongoosa obulamu bw’emisuwa n’emisuwa gy’abalwadde abagejjulukuka okuyita mu makubo agawerako. Okugeza, okukendeeza ku miwendo egitali gya HDL-C, apoB, ne LDLP kiyinza okukendeeza ku bulabe bw’okuzimba emisuwa; okukendeeza ku miwendo gya glycated hemoglobin kiyinza okulongoosa okufuga glucose mu musaayi mu balwadde ba sukaali, bwe kityo ne kikendeeza ku bulabe bw’ebizibu by’emisuwa [3, 5, 6]..
Obujjanjabi bw’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge (NAFLD): Retatrutid ye peptide empya ey’okukwata ebitundu bisatu etunuulira ekirungo kya glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), n’ekirungo kya glucagon-like peptide-1 receptor (GLP-1R). Okunoonyereza kulaga nti Retatrutid erina obusobozi okujjanjaba obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Mu kunoonyereza okumu, okugezesebwa okwa randomized, double-blind, placebo-controlled trial kwakolebwa okumala wiiki 48 ku beetabye mu kugezesebwa abalina obulwadde bw’ekibumba obw’amasavu obukwatagana n’obutakola bulungi mu nkyukakyuka y’emmere n’amasavu mu kibumba aga ≥10%. Ebivuddemu biraga nti ku wiiki 24, enkyukakyuka ez’enjawulo mu masavu g’ekibumba okuva ku ntandikwa mu beetabye mu kujjanjabwa ne dose ez’enjawulo eza Retatrutid (1mg, 4mg, 8mg, ne 12mg) zaali -42.9%, -57.0%, -81.4%, ne -82.4%, okusinziira ku, ate nga mu kibinja kya placebo yali +0.3% [7] . Kino kiraga nti Retatrutid eyinza okuba n’akakwate akakulu mu bujjanjabi ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge.
Mu kumaliriza, nga novel triple receptor agonist, Retatrutid eraga obusobozi bungi mu kujjanjaba omugejjo n’endwadde ezikwatagana nabyo. Kisobola okulung’amya enkyukakyuka y’omubiri gw’omuntu okuva mu bipimo ebingi nga kikola ekirungo kya glucagon, ekikwata insulinotropic polypeptide eyeesigama ku glucose, n’ekirungo kya peptide-1 ekiringa glucagon, okulongoosa okufuga glucose mu musaayi, okukendeeza ku buzito bw’omubiri, n’okutereeza enkyukakyuka y’amasavu. Okuvaayo kwa Retatrutid kuleese enkola empya ez’obujjanjabi eri abalwadde abagejjulukuka, ssukaali ow’ekika eky’okubiri, n’ebirala Kisuubirwa okumenyawo obuzibu bw’eddagala ery’ekinnansi erya single receptor agonist, okuwa ekyokulwanyisa eky’amaanyi ennyo eky’okugonjoola ebizibu ebyeyongera okuba eby’amaanyi eby’omugejjo n’endwadde z’enkyukakyuka mu mubiri, okutumbula okwongera okukulaakulanya eby’obujjanjabi ebikwatagana nabyo, okutumbula omutindo gw’obulamu bw’abalwadde, n’okukendeeza ku bujjanjabi bw’embeera z’abantu omugugu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Rosenstock J mukenkufu alina obuyinza bungi mu by’obusawo, ng’akolagana nnyo n’amatendekero nga University of Texas Southwestern Medical Center ne University of Texas Dallas. Akola n’okunoonyereza mu bifo nga Canadian VIGOR Center ne Veloc Clin Res Ctr Med City.
Okunoonyereza kwe kukwata ku endocrinology and metabolism, cardiovascular system and cardiology, pharmacology, n’eddagala ery’okugezesa, ng’essira aliteeka ku ssukaali, omugejjo, n’obujjanjabi obukwatagana nabyo n’okukola eddagala. J Rosenstock atuuse ku buwanguzi obw’amaanyi mu busawo obw’obujjanjabi, n’alondebwa okuba Highly Cited Researcher okuva mu 2017 okutuuka mu 2024. Kino kiraga nti omulimu gwe gukwata nnyo n’okusiimibwa mu bugazi. Ng’ayita mu nkolagana n’ebitongole by’okunoonyereza ebiwerako, avvuunudde bulungi ebizuuliddwa mu kunoonyereza okusookerwako mu kukozesebwa mu bujjanjabi, n’aganyula abalwadde abalina endwadde z’enkyukakyuka mu mubiri n’emisuwa n’okutumbula ssaayansi w’obusawo. Rosenstock J awandiikiddwa mu kiwandiiko ekijuliziddwa [4].
▎ Ebiwandiiko Ebikwatagana
[1] Kaur M, Misra S. Okuddamu okwetegereza eddagala erinoonyereza erya retatrutide, ekirungo ekipya eky’ekika kya triple agonist ekijjanjaba omugejjo[J]. European Journal of Clinical Pharmacology, 2024,80 (5): 669-676.DOI: 10.1007 / s00228-024-03646-0.
[2] Jastreboff A. M., Kaplan L. M., Frias J. P., n’abalala. Triple-Hormone-Receptor Agonist Retatrutid ku mugejjo - Okugezesebwa okw'omutendera ogw'okubiri[J]. New England Journal of Eddagala, 2023,389 (6): 514-526.DOI: 10.1056 / NEJMoa2301972.
[3] Lopez D. C., Pajimna J. T., Milan M. D., n’abalala. 7792 Obulung’amu bwa Retatrutid okukendeeza ku buzito n’ebikosa byayo mu mutima mu bantu abakulu: Okwekenenya okutegekeddwa n’okwekenneenya okutambula[J]. Journal of Ekibiina ky'Endocrine, 2024,8 (1): 163-749.DOI: 10.1210 / jendso / bvae163.749.
[4] Rosenstock J, Frias J, Jastreboff A. M., n’abalala. Retatrutid, GIP, GLP-1 ne glucagon receptor agonist, eri abantu abalina sukaali ow’ekika eky’okubiri: okugezesebwa okwakolebwa mu USA[J]. Lancet, 2023,402 (10401): 529-544.DOI: 10.1016 / S0140-6736 (23) 01053-X.
[5] Nicholls S, Pirro V, Lin Y, n’abalala. Triple-hormone receptor agonist retatrutide erongoosa nnyo lipoprotein ne apolipoprotein profiles mu beetabye mu kugezesebwa abalina omugejjo oba omugejjo omungi[J]. Ekitabo ky’omutima ekya Bulaaya, 2024,45.DOI:10.1093/eurheartj/ehae666.1501.
[6] Ray A. Retatrutid: eddagala erikwata eddagala lya incretin ery’emirundi esatu erijjanjaba omugejjo[J]. Endowooza y'abakugu ku ddagala erinoonyereza, 2023,32(11):1003-1008.DOI:10.1080/13543784.2023.2276754.
[7] Sanyal A. J., Kaplan L. M., Frias J. P., n’abalala. Triple hormone receptor agonist retatrutide ku bulwadde bw’ekibumba obukwatagana n’obutakola bulungi mu nkyukakyuka y’emmere: okugezesebwa okw’omutendera 2a okutali kwa bulijjo[J]. Eddagala ly’obutonde, 2024, 30 (7): 2037-2048.DOI: 10.1038 / s41591-024-03018-2.
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.