Bya Cocer Peptides 
emyezi 2 egiyise
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.
Ng’endwadde z’enkyukakyuka mu mubiri ng’omugejjo, omugejjo, ne ssukaali bweyongera okweyongera mu nsi yonna, okunoonya eddagala erisinga okukola obulungi ku bujjanjabi kifuuse ensonga enkulu mu by’obusawo. Mazdutide, nga novel dual receptor agonist, esobola okukola mu kiseera kye kimu GLP-1 receptor ne glucagon receptor, era esuubirwa okukola omulimu ogw’enjawulo mu kugejja n’okufuga ssukaali mu musaayi, okuwa emikisa emipya egy’okujjanjaba endwadde z’enkyukakyuka mu mubiri.
Ekifaananyi 1 Ensengekera y’eddagala lya Mazdutide.
Okulaba ebikwata ku Mazdutide
Mazdutide ddagala lya GLP-1/glucagon dual receptor agonist, eddagala eppya erijjanjaba endwadde z’enkyukakyuka mu mubiri. Mu myaka egiyise, okukola eddagala nga kigendereddwamu endwadde z’enkyukakyuka mu mubiri kweyongedde okugenda mu maaso. GLP-1 receptor agonists ne glucagon receptor agonists ziraze ebimu ku bikolwa eby’obujjanjabi nga zikozesebwa zokka, naye era zirina obuzibu bwazo. Okunoonya obujjanjabi obusingako obulungi, abanoonyereza essira balitadde ku kukola eddagala eriyinza okukola ku bigendererwa ebingi omulundi gumu, ekivaako okutondebwawo kwa Mazdutide. Enkola yaayo ey’okugikulaakulanya ebadde mu kunoonyereza okw’amaanyi nga tekunnabaawo n’okugezesebwa mu bujjanjabi okw’emitendera mingi, nga mpolampola ekakasa obukuumi bwayo n’obulungi bwayo.
Enkola y’Ekikolwa
(1) Okukola kwa GLP-1 Receptor
Okulungamya enkola ya glucose mu musaayi: GLP-1 ye peptide hormone efulumizibwa obutoffaali bwa L obw’ekyenda. Oluvannyuma lw’okukola ekirungo kya GLP-1, Mazdutide etereeza glucose mu musaayi ng’eyita mu makubo agawerako. Kitumbula okufulumya insulini obutoffaali bwa β mu lubuto, kyongera ku kuwulira kwa insulini, bwe kityo ne kyanguya okutwala glucose n’okukozesa, n’okukendeeza ku glucose mu musaayi. Kiziyiza okufulumya glucagon okuva mu butoffaali bwa α obw’olubuto era kikendeeza ku glucose efuluma mu kibumba, okwongera okukuuma glucose mu musaayi ng’anywevu.
Okulwawo okufulumya amazzi mu lubuto: Mazdutide ekola ku GLP-1 receptor, ekola ku busimu bw’omu lubuto okukendeeza ku kufulumya amazzi mu lubuto. Kino kiwangaaza emmere okusigala mu lubuto, ne kyongera okukkuta n’okukendeeza ku mmere gy’olya, bwe kityo ne kiyamba okufuga omugejjo.
Okulungamya okwagala okulya: Oluvannyuma lw’okukola kw’ekirungo kya GLP-1, obubonero buyisibwa mu nkola y’obusimu obw’omu makkati, nga bukola ku kifo eky’okuliisa ekya hypothalamic okulung’amya okufulumya kw’obusimu obuyitibwa neuropeptides obukwatagana n’okwagala okulya, gamba ng’okukendeeza ku kwolesebwa kwa neuropeptide Y (NPY) n’okwongera ku kwolesebwa kwa proopiomelanocortin (POMC), bwe kityo ne kireeta okuwulira ng’ojjudde n’okukendeeza ku kulya emmere.
(2) Okukola kw’ebikwata ku glucagon
Okutumbula ensaasaanya y’amasoboza: Ekirungo kya glucagon bwe kikolebwa Mazdutide, kitumbula okumenya amasavu n’okufuuka asidi w’amasavu, ekyongera ku nsaasaanya y’amasoboza. Okugatta ku ekyo, upregulates expression of uncoupling protein 1 (UCP1), okutumbula thermogenesis mu brown adipose tissue, okwongera okutumbula omubiri okukyusakyusa amaanyi n’okuyamba mu kugejja.
Okulungamya enkyukakyuka ya glucose: Okukola kw’ebikwata glucagon kitumbula hepatic glycogenolysis ne gluconeogenesis. Naye, wansi w’obuyinza bwa Mazdutide, kino ekikolwa eky’okutumbula tekikoma ku kusitula miwendo gya glucose mu musaayi wabula mu kifo ky’ekyo kituuka ku kulungamya kwa glucose mu musaayi okutuufu okuyita mu nkolagana ey’okukwatagana n’ebikolwa by’okukola kwa GLP-1 receptor. Emiwendo gya glucose mu musaayi bwe giba mingi, ekikolwa ky’okukendeeza sukaali ekitabaganyizibwa okukola kwa GLP-1 receptor kye kisinga; bwe kiba nti emiwendo gya glucose mu musaayi giba wansi, ekikolwa ky’okulinnya kwa sukaali ekitabaganyizibwa okukola kw’ekirungo kya glucagon receptor kiziyiza okukendeera kwa sukaali mu musaayi.
(3) Enkola y’okukwatagana
Mazdutide mu kiseera kye kimu ekola ebitundu byombi ebikwata GLP-1 n’ebikwata glucagon. Amakubo g’obubonero agakozesebwa ebirungo bino ebibiri gakola mu ngeri ey’okukwatagana okukola ekikolwa ekisingawo ekijjuvu era eky’amaanyi eky’okulungamya enkyukakyuka y’emmere. Mu nsonga z’okugejja, okukola kwa GLP-1 receptor kukendeeza ku maanyi agayingira nga kunyigiriza okwagala okulya n’okulwawo okufulumya amazzi mu lubuto, ate okukola kwa glucagon receptor kutumbula ensaasaanya y’amaanyi. Ekikolwa ky’okukwatagana kw’ebikwata byombi kituuka bulungi nnyo ku kukendeeza ku buzito. Mu nsonga y’okulungamya glucose mu musaayi, ebiva mu kukola kwa receptor zombi bikwatagana okukuuma glucose mu musaayi mu bbanga erya bulijjo n’okwewala enkyukakyuka eziyitiridde.
3. Ebikosa mu mubiri
(1) Ebiva mu kugejja
Obujulizi obw’obujjanjabi: Okugezesebwa okw’obujjanjabi okungi kulaga nti Mazdutide alina ebikosa ebinene mu kugejja. Mu kunoonyereza okwagenderera abantu abakulu abagejjulukuka oba abagejjulukuka mu , wiiki 24 ez’obujjanjabi bwa Mazdutide (nga dose esinga obunene ya 6 mg) kyavaamu okugejja kwa wakati okwa 6.7%–11.3%, ate ekibinja kya placebo kyafuna okweyongera kw’obuzito 1.0%. Mu bibinja bya ddoozi ez’enjawulo, Mazdutide ku 4.5 mg ne 6 mg yalaga ebikolwa ebisinga okweyoleka mu kugejja, ng’enjawulo mu bujjanjabi bw’ogeraageranya ne placebo yali wakati wa -7.7% okutuuka ku -12.3% (P < 0.0001). Mu kwekenneenya okutegekeddwa n’okusengejja (meta-analysis) okwali kuzingiramu abeetabye mu kugezesebwa 680, Mazdutide yalaga enkizo ennene ku placebo mu kukendeeza ku buzito, ng’enjawulo ya wakati (MD) ya -6.22% (95% confidence interval [CI]: -8.02% okutuuka ku -4.41%).
Ekifaananyi 2 Enkomerero z’obuzito bw’omubiri. a Enkyukakyuka mu bitundu ku kikumi okuva ku ntandikwa mu buzito bw’omubiri mu wiiki 24. b Enkyukakyuka mu bitundu ku kikumi okuva ku ntandikwa mu buzito bw’omubiri okumala ekiseera.
(2) Ebiva mu kulungamya Glycemic
Ebikosa abalwadde ba ssukaali ow’ekika eky’okubiri: Ku balwadde ba sukaali ow’ekika eky’okubiri, Mazdutide ekendeeza bulungi hemoglobin A1c (HbA1c) ne glucose mu musaayi mu kisiibo. Mu kugezesebwa okukwatagana okwa randomized, double-blind, placebo-controlled Phase 2 clinical trial, abalwadde abalina sukaali ow’ekika eky’okubiri abaafuna obujjanjabi bwa Mazdutide (ku ddoozi esinga obunene eya 6 mg) okumala wiiki 20, baalaga enkyukakyuka eya wakati mu HbA1c okuva ku -1.41% okutuuka ku -1.67%, ate ekibinja kya placebo kyalaga enkyukakyuka ya 0.03%, nga waliwo enjawulo enkulu mu bibalo bw’ogeraageranya n’eddagala erya placebo (P < 0.0001). Abalwadde era baafuna okukendeera okw’amaanyi mu buzito bw’omubiri, ng’enkyukakyuka ya wakati ku buli kikumi eraga enkolagana eyesigamiziddwa ku ddoozi, okutuuka ku -7.1%.
Ebirungi mu kulungamya glucose mu musaayi: Mazdutide tekoma ku kukendeeza ku glucose mu musaayi wabula era alongoosa enkyukakyuka ya glucose mu musaayi n’okukendeeza ku bulabe bw’okukendeera kwa glucose mu musaayi. Bw’ogeraageranya n’eddagala ery’ekinnansi eriweweeza ku ssukaali, enkola yaayo eya dual receptor agonist etuuka ku kulungamya kwa glucose mu musaayi okutuufu era okujjuvu, bwe kityo ne kilongoosa omutindo gw’obulamu bw’abalwadde n’okuteebereza okw’ekiseera ekiwanvu.
(3) Ebikosa ebiraga emisuwa n’enkyukakyuka y’emmere
Okutereeza puleesa: Mazdutide ekendeeza puleesa ya systolic ne diastolic. Okwekenenya okutegekeddwa n’okwekenneenya okutambula (meta-analyses) kulaga nti bw’ogeraageranya ne placebo, Mazdutide ekendeeza puleesa ya systolic n’enjawulo eya wakati (MD) eya -7.57 mmHg (95% CI: -11.17 okutuuka ku -3.98 mmHg); ku kukendeeza puleesa mu diastolic, MD yali -2.98 mmHg (95% CI: -5.74 okutuuka ku -0.22 mmHg). Kino kiyinza okuva ku nkola za Mazdutide eziwera, omuli okulongoosa enkola y’emisuwa endothelial, okukendeeza ku buziyiza bw’emisuwa egy’okumpi, n’okulungamya bbalansi y’amazzi ne sodium.
Okulungamya amasavu: Mazdutide etereeza bulungi ebifaananyi by’amasavu. Kikendeeza ku kolesterol yenna (MD = -16.82%, 95% CI: -24.52 okutuuka ku -9.13%), triglycerides (MD = -43.29%, 95% CI: -61.57 okutuuka ku -25.01%), ne lipoprotein eya density entono (MD = -17.07%, 95% CI: -25.54 okutuuka ku -8.60%). emitendera, ate nga era ekola ekikolwa ekimu eky’okulungamya ku lipoprotein eya density enkulu (MD = -7.54%, 95% CI: -11.26 okutuuka ku -3.83%). Ebikolwa bino biyamba okukendeeza ku bulabe bw’endwadde z’emisuwa era biba n’ekikolwa eky’obukuumi ku nkola y’emisuwa.
(4) Ebikosa obulwadde bwa hyperuricemia
Obujulizi obw’okugezesa ebisolo: Mu kunoonyereza okwakolebwa ku nvunza eya hyperuricemia (HUA), okukuba empiso ya Mazdutide 0.05 mg/kg ne 0.075 mg/kg wansi w’olususu (buli nnaku 3) yakendeeza nnyo ku miwendo gya serum uric acid (SUA) mu nvunza. Bw’ogeraageranya n’ekibinja kya HUA, emiwendo gya SUA ne serum creatinine (SCr) gyakendeera nnyo mu kibinja kya Maz-MD ne Maz-HD, ate emiwendo gya protein mu musulo (U-Pro) nagyo gyakendeera nnyo mu kibinja kya Maz-MD. Okugatta ku ekyo, Mazdutide yalongoosa enkyukakyuka mu kibumba histopathological mu nvunza HUA.
Ekifaananyi 3 a: Enkyukakyuka mu bitundu ku kikumi okuva ku ntandikwa mu buzito bw’omubiri okumala ekiseera. b: Ekitundu ky‟abeetabye mu kutendekebwa kuno abatuuka ku biruubirirwa by‟okugejja.
Okunoonyereza ku nkola y’okukozesa
(1) Enkulaakulana y’okugezesebwa mu bujjanjabi
Okugezesebwa okw’obujjanjabi okwasooka: Okugezesebwa okw’obujjanjabi okwasooka okwa Phase 1 okusinga kwakebera obukuumi, okugumiikiriza, n’obulungi bwa Mazdutide obusookerwako. Mu kugezesebwa okwa randomized, placebo-controlled, multiple-dose escalation Phase 1b trial, abantu abakulu abaali omugejjo oba omugejjo baweebwa dose ez’enjawulo eza Mazdutide (okutuuka ku 10 mg). Ebivuddemu biraga nti Mazdutide yagumiikiriza bulungi mu ddoozi eno, nga tewali buzibu bwa maanyi bwaloopebwa, era okugejja okw’amaanyi kwalabiddwa.
Phase 2 clinical trial: Phase 2 clinical trial yayongera okukakasa obulungi n’obukuumi bwa Mazdutide mu bantu ab’enjawulo. Mu kugezesebwa okwa Phase 2 okwagenderera abalwadde b’e China abalina ssukaali ow’ekika eky’okubiri, Mazdutide yalaga ebikolwa ebinene mu kukendeeza HbA1c n’obuzito bw’omubiri, ng’obukuumi bugeraageranyizibwa ku kibinja kya placebo. Ebizibu ebyatera okubaawo okusinga byali bizibu ebitono oba eby’ekigero mu lubuto, gamba ng’ekiddukano n’okuziyira. Mu kugezesebwa okw’omutendera ogw’okubiri okwagenderera abantu abakulu abagejjulukuka oba abagejjulukuka, wiiki 24 ez’obujjanjabi bwa Mazdutide (okutuuka ku 6 mg) zalaga nti kikola bulungi mu kugejja n’obukuumi.
(2) Okunoonyereza okugeraageranya n’eddagala eddala
Okugerageranya ne GLP-1 receptor agonists: Bw’ogeraageranya ne GLP-1 receptor agonists ez’ekinnansi, Mazdutide eyinza okuba n’ebikosa ebinene ku kugejja n’okulungamya glucose mu musaayi olw’okukola kwayo emirundi ebiri GLP-1 receptors ne glucagon receptors. Mu kunoonyereza okumu, Mazdutide yatuuka ku kugejja okusinga ku GLP-1 receptor agonists ezimu mu kiseera kye kimu eky’obujjanjabi era yalaga okutebenkera okw’ekika ekya waggulu mu kufuga glucose mu musaayi.
Okugeraageranya n’eddagala eddala eriweweeza ku ssukaali: Bw’ogeraageranya n’eddagala ery’ekinnansi eriweebwa mu kamwa, Mazdutide tekoma ku kukendeeza bulungi glucose mu musaayi wabula era ekuwa emigaso emirala ng’okugejja n’okulongoosa obubonero bw’enkyukakyuka y’emisuwa gy’omutima.
Mu bufunzi
Nga GLP-1/glucagon dual receptor agonist, Mazdutide etuuka ku kulungamya okujjuvu okw’okukyusakyusa amaanyi, glucose mu musaayi, puleesa, n’amasavu mu musaayi nga mu kiseera kye kimu ekola ebirungo bibiri ebikulu ebikwata ku kulungamya metabolic, eraga ebikolwa eby’obujjanjabi ebijjuvu era eby’amaanyi okusinga agonists ezikwata emu. Mazdutide alina ekisuubizo kinene ku buzibu obw’enjawulo mu nkyukakyuka y’emmere, omuli omugejjo, sukaali ow’ekika eky’okubiri, ne hyperuricemia.
Ensonda
[1] Zhang B, Cheng Z, Chen J, n’abalala. Obulung’amu n’obukuumi bwa Mazdutide mu balwadde b’Abachina abalina sukaali ow’ekika eky’okubiri: Okugezesebwa okwa Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial[J]. Okulabirira obulwadde bwa sukaali, 2024,47 (1): 160-168.DOI: 10.2337 / dc23-1287.
[2] Nalisa D. L., Cuboia N., Dyab E., n’abalala. Obulung’amu n’obukuumi bwa Mazdutide ku kugejja mu balwadde ba ssukaali n’abatali ba ssukaali: okwekenneenya okutegekeddwa n’okwekenneenya okugezesebwa okufugibwa okutali kwa bulijjo[J]. Ensalo mu Endocrinology, 2024,15. https://api.semanticscholar.org/CorpusID:267984513. Enkola y’okukuuma obutonde bw’ensi.
[3] Ji L, Jiang H, Cheng Z, n’abalala. A phase 2 randomized controlled trial of mazdutide mu China abantu abakulu abagejjulukuka oba abantu abakulu abalina omugejjo[J]. Empuliziganya y’obutonde, 2023, 14 (1): 8289.DOI: 10.1038 / s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: Omupya Glucagon-Like Peptide-1 (GLP-1R) ne Glucagon (GCGR) Receptor Dual Agonist, Mazdutide (IBI362), Akendeeza ku Hyperuricemia mu Nvunza ezirina Hyperuricemic[J]. Ssukaali, 2023. Enkola y’okukuuma obutonde bw’ensi mu bitundu by’eggwanga eby’enjawulo
[5] Ji L, Gao L, Jiang H, n’abalala. Obukuumi n’obulungi bw’eddagala lya GLP-1 ne glucagon receptor dual agonist mazdutide (IBI362) 9 mg ne 10 mg mu bantu abakulu Abachina abagejjulukuka oba abagejjulukuka: Okugezesebwa okwa randomised, placebo-controlled, multiple-ascending-dose phase 1b trial[J]. Eddagala ly’obujjanjabi, 2022,54:101691.DOI:10.1016/j.eclinm.2022.101691.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
