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1kits (Ebipipa 10) .
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▎ Enzimba ya Mazdutide
Ensibuko: PubChem |
Omutendera: AEGTFTSDVSSYLEGQAAKFIAWLVKGRG Ensengekera ya molekyu: C 207H 317N 45O65 Obuzito bwa molekyu: 4476g/mol Ennamba ya CAS: 2259884-03-0 PubChem CID: 167312357. Omuntu w’abantu Ebigambo ebifaanagana: GLXC-26803 |
▎ Okunoonyereza ku Mazdutide
Mazdutide okunoonyereza kuliko ki?
Ensonga enkulu ey’omugejjo mu nsi yonna n’endwadde ezikwatagana nabyo:
Omugejjo n’omugejjo byeyongedde okusoomoozebwa okw’amaanyi mu by’obulamu bw’abantu mu nsi yonna. Okusinziira ku World Obesity Atlas, omuwendo gw’abantu abagejjulukuka mu nsi yonna gwatuuka ku bukadde 764 mu 2020 era nga gusuubirwa okulinnya okutuuka ku kawumbi kamu mu mwaka gwa 2030. Omugejjo guyinza okuleeta ebizibu by’obulamu bingi, gamba ng’endwadde z’emisuwa n’obulwadde bwa sukaali obw’ekika eky’okubiri, ebikosa ennyo omutindo gw’obulamu bw’omuntu ssekinnoomu n’ebikozesebwa mu by’obujjanjabi mu nsi yonna. Kino kireetedde abanoonyereza okunoonyereza ku nkola ennungi ez’obujjanjabi naddala eddagala eppya.
Omusingi gw’enkulaakulana y’eddagala erikolebwa mu incretin:
Okuva endowooza ya incretin lwe yateesebwako mu 1932, okunoonyereza okukwatagana nabyo kubadde kugenda mu maaso buli lukya. Mu 1987, GLP-1 yazuulibwa ng’ekikulu ekifuga okufulumya insulini mu lubuto, era enkola z’obujjanjabi bwa sukaali ow’ekika eky’okubiri nga zeesigamiziddwa ku incretin zakolebwa. Mu 2005, exenatide, eddagala erisooka mu nsi yonna erya GLP-1 receptor agonist (GLP-1RA), lyakkirizibwa okutundibwa, ne liteekawo omusingi omunywevu ogw’enzikiriziganya n’enkola ey’okunoonyereza n’okukola eddagala eppya erisinziira ku incretin nga Mazdutide. Mazdutide ye analog ya oxyntomodulin y’ebisolo ebiyonka (OXM). Ng’omulembe omupya ogw’ekika kya dual agonist ogugenderera GLP-1R ne GCGR, erina enkola ey’enjawulo ey’okukola emirundi ebiri n’essuubi ddene mu kujjanjaba okugejja n’endwadde ezikwatagana nabyo.
Enkola ya Mazdutide ekola ki?
Agonistic effect ku glucagon-like peptide-1 (GLP-1) ekirungo ekikwata:
GLP-1 ye hormone y’ekyenda esobola okutumbula okufulumya insulin n’okuziyiza okufulumya glucagon mu ngeri eyeesigama ku bungi bwa glucose, bwe kityo ne kikendeeza ku glucose mu musaayi [1] . Nga GLP-1 receptor agonist, Mazdutide ekoppa ekikolwa kya GLP-1, okutumbula okufulumya insulini n’okukendeeza ku kufulumya glucagon, ekiyamba okutereeza glucose mu musaayi. Ekirala, GLP-1 receptor agonists zisobola okulwawo okufulumya amazzi mu lubuto, okutumbula okukkuta, n’okukendeeza ku mmere gye balya, ekintu eky’omugaso mu kufuga obuzito [1, 2]..
Ekikolwa kya agonistic ku kirungo kya glucagon:
Glucagon asobola okutumbula okumenya kwa glycogen mu kibumba ne gluconeogenesis, ekivaako glucose mu musaayi okweyongera. Mazdutide, nga ekola ku glucagon receptor, esobola okulung’amya ensonga eziwerako ez’enkyukakyuka ya glucose, okutuuka ku kulungamya okulungi okwa glucose mu musaayi. Glucagon era etumbula lipolysis, eyamba okukendeeza amasavu okukuŋŋaanyizibwa n’okukendeeza ku buzito bw’omubiri [1, 2]..
Enkola y’okulungamya ku puleesa:
Mazdutide asobola okukendeeza puleesa ya systolic ne diastolic. Ku ludda olumu, ekendeeza puleesa ng’etereeza enkyukakyuka ya glucose n’amasavu n’okulongoosa enkola y’emisuwa endothelial; ku ludda olulala, kiyinza okukosa enkola z’okulungamya puleesa ng’enkola ya renin-angiotensin.
Enkola ki entongole eya Mazdutide ey’okugejja?
Okulungamya glucose mu musaayi n’enkyukakyuka mu mubiri:
Nga agonist ey’emirundi ebiri eya glucagon-like peptide-1 (GLP-1) ne glucagon receptors, ekimu ku bikolwa ebingi eby’omubiri ebya GLP-1 kwe kulungamya emiwendo gya glucose mu musaayi. Kitumbula okufulumya insulini, kiziyiza okufulumya glucagon, kikendeeza ku glucose mu musaayi [1] , kilwawo okufulumya amazzi mu lubuto, kyongera okukkuta, n’okukendeeza ku mmere. Ate Glucagon ayamba okuzimba amasavu n’okukozesa amaanyi. N’olwekyo, Mazdutide ekola ku bikwata byombi n’okutereeza enkyukakyuka ya glucose mu musaayi okutuuka ku kugejja. Okunoonyereza kulaga nti Mazdutide esobola okukendeeza ku buzito bw’omubiri, puleesa (systolic ne diastolic), total cholesterol, triglycerides, low-density lipoprotein, ne high-density lipoprotein levels [3] , ekiraga nti esobola okuvaako okugejja n’okulongoosa obuzibu bw’enkyukakyuka mu mubiri obuva ku mugejjo.
Enkola ku njagala y’okulya n’okukozesa amaanyi:
Mazdutide ayinza okutuuka ku kugejja ng’akwata ku njagala y’okulya n’amaanyi g’onywa. Mu kugezesebwa okumu okw’obujjanjabi, abeetabye mu kugezesebwa baafuna ebizibu by’omu lubuto ng’okukendeera kw’okwagala okulya oluvannyuma lw’okukozesa Mazdutide [3] . Kino kiyinza okuva ku kukola obutereevu kwa Mazdutide ku nkola y’olubuto oba okuyita mu kulungamizibwa kw’obusimu obw’omu makkati. Ka kibeere nti enkola etya, okukendeeza ku njagala y’okulya n’ebizibu ebiva mu lubuto kijja kukendeeza ku maanyi g’onywa n’okutumbula okugejja. Okugatta ku ekyo, Mazdutide eyinza okukosa okwagala okulya ng’etereeza obusimu obutambuza obusimu n’obusimu mu bwongo. Okugeza, GLP-1 esobola okukola ku hypothalamus okutereeza okwagala okulya n’okutebenkeza amaanyi [4]..
Makubo ki ag’enjawulo agakola Mazdutide mu kulungamya glucose mu musaayi?
Okusitula okufulumya insulini:
Glucagon-like peptide-1 (GLP-1) receptor agonists zisobola okusitula okufulumya insulini. Nga agonist ey’emirundi ebiri eya GLP-1 ne glucagon receptors, Mazdutide eyinza okukola GLP-1 receptor okuleetera obutoffaali bwa pancreatic islet β okufulumya insulin. Insulin busimu bukulu mu kukendeeza glucose mu musaayi, ekiyinza okutumbula obutoffaali okutwala glucose n’okukendeeza ku glucose mu musaayi [1]..
Okuziyiza okufulumya glucagon:
Mu kiseera kye kimu, Mazdutide eyinza okukola ku glucagon receptor okuziyiza okufulumya glucagon. Glucagon ne insulin biziyizagana mu kulungamya glucose mu musaayi, era okukendeeza ku kufuluma kwayo kiyamba okukendeeza glucose mu musaayi [1]..
Okulungamya enkyukakyuka ya glucose:
Mazdutide eyinza okutereeza enkyukakyuka ya glucose ku mitendera mingi okukozesa ekikolwa kyayo eky’okukendeeza sukaali, gamba ng’okukosa enkyukakyuka ya glucose mu kibumba, ebinywa, n’ebitundu by’amasavu. Mu kibumba, kikendeeza ku kumenyaamenya kwa glycogen mu kibumba ne gluconeogenesis, ekikendeeza ku kukola glucose mu musaayi; mu bitundu by’ebinywa, kitumbula okutwalibwa n’okukozesa glucose; mu bitundu by’amasavu, kitereeza enkyukakyuka y’amasavu, kikendeeza ku kufulumya asidi z’amasavu ez’obwereere, era kikosa glucose mu musaayi mu ngeri etali butereevu [1, 3]..
Enkola ku njagala y’okulya n’okukozesa amaanyi:
Okunoonyereza kuzudde nti Mazdutide esobola okukendeeza ku njagala y’okulya n’amaanyi g’anywa, nga kiyinzika okuba ng’akola ku bikwata mu busimu obw’omu makkati n’okulungamya ekkubo ly’obubonero bw’okulya. Okukendeeza ku mmere gye balya kiyinza okukendeeza ku nsibuko ya glucose mu musaayi n’okuyamba okufuga glucose mu musaayi [3, 5]..
Enkyukakyuka okuva ku ntandikwa mu buzito bw’omubiri n’okwetooloola ekiwato.
a.Enkyukakyuka mu bitundu ku kikumi okuva ku ntandikwa mu buzito bw’omubiri okumala ekiseera. b. Enkyukakyuka okuva ku ntandikwa mu buzito bw’omubiri okumala ekiseera.
Ensibuko:PubMed [2] .
Mazdutide ekozesebwa ki?
Obujjanjabi bwa sukaali ow’ekika eky’okubiri:
Okugezesebwa okwa randomized, double-blind, placebo-controlled Phase 2 trial kwalaga nti Mazdutide, eddagala ery’emirundi ebiri eriweebwa buli wiiki erya glucagon-like peptide 1 (GLP-1) ne glucagon receptors, yalaga obulungi n’obukuumi mu balwadde b’Abachina abalina sukaali ow’ekika eky’okubiri [1]..
Okukozesa mu kugejja:
Okunoonyereza ku balwadde abalina ssukaali n’abatalina: Okwekenenya okutegekeddwa n’okusengejja (meta-analysis) kwalaga nti Mazdutide esobola bulungi okukendeeza ku buzito bw’omubiri gw’abantu abakulu abalina oba abatalina ssukaali [3] . Okunoonyereza kuno kwalimu okugezesebwa musanvu okwakolebwa mu ngeri ey’ekifuulannenge nga kuliko abantu 680. Ebivuddemu biraga nti bw’ogeraageranya n’eddagala erya placebo, Mazdutide yaleetawo okukendeera okw’amaanyi mu buzito bw’omubiri (enjawulo wakati [MD] = -6.22%, 95% confidence interval [CI]: -8.02% okutuuka ku -4.41%, I⊃2; = 90.0%) (Nalisa DL, 2024). Okwekenenya mu kibinja ekitono ne meta-regression kwazuula nti abalwadde abatalina sukaali baali bakendedde nnyo mu buzito, era abalwadde abajjanjabiddwa okumala wiiki 24 baalina okukendeera kw’obuzito okweyoleka bw’ogeraageranya n’abo abajjanjabwa okumala wiiki 12 - 20 [3]..
Okukozesa mu bantu abakulu Abachina abagejjulukuka oba abagejjulukuka:
Okwekenenya okw’omu makkati okw’okugezesebwa okwakolebwa mu ngeri ey’ekifuulannenge, okw’ebitundu bibiri (ddoozi entono okutuuka ku 6mg ne ddoozi enkulu 9mg), okugezesebwa okw’emirundi ebiri, okufugibwa placebo okwa Phase 2 okwakolebwa mu bantu abakulu Abachina abagejjulukuka oba abagejjulukuka kwalaga nti Mazdutide yali ya bulabe era ekola bulungi mu bantu bano mu kiseera ky’obujjanjabi ekya wiiki 24, ekyaleeta okugejja okw’amaanyi era okw’amakulu mu bujjanjabi [2] . Mu kunoonyereza, abantu abakulu abagejjulukuka (BMI ≥ 24 kg/m²) nga bawerekerwako hyperphagia ne/oba waakiri comorbidity emu eyeekuusa ku mugejjo, oba abantu abakulu abalina omugejjo (BMI ≥ 28 kg/m²) baaweebwa mu ngeri ey’ekifuulannenge okufuna Mazdutide buli wiiki ku ddoozi za 3mg, 4.5mg, 6mg oba a okukwatagana ne placebo. Ebivuddemu biraga nti okuva ku ntandikwa okutuuka mu wiiki ey’amakumi abiri mu ena, enkyukakyuka mu buzito bw’omubiri mu bitundu 100 ku 100 yali -6.7% (standard error 0.7) mu kibinja kya 3mg Mazdutide, -10.4% (0.7) mu kibinja kya 4.5mg, -11.3% (0.7) mu kibinja kya 6mg, ne 1.0% (0.7) mu kibinja kya placebo. Bw’ogeraageranya ne placebo, enjawulo mu bujjanjabi yali wakati wa -7.7% okutuuka ku -12.3% (zonna p < 0.0001) [2]..
Mu kumaliriza, ng’eddagala eriyiiya erya dual-target agonist, okuyita mu nkola eziwera nga okulungamya glucose mu musaayi, okutumbula metabolism y’amasavu, n’okuziyiza appetite, Mazdutide esobola bulungi okulongoosa glucose mu musaayi gw’abalwadde ba sukaali ow’ekika eky’okubiri n’okuyamba abantu abagejjulukuka okugejja. Kifuyira amaanyi amapya mu kujjanjaba endwadde z’enkyukakyuka mu mubiri era kisuubirwa okukendeeza ku buzito bw’ensi yonna obw’omugejjo n’endwadde ezikwatagana nabyo.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Zhang B mukenkufu alina ebisaanyizo eby’amaanyi ng’akwatagana n’ebibiina ebingi eby’ettutumu. Mu bino mulimu Peking Union Medical College, Chinese Academy of Medical Sciences -Peking Union Medical College, - Japan Friendship Hospital, Guizhou Equipment Mfg Polytech, Shanghai Jiao Tong University, Universiti Utara Malaysia, Yingkou Institute of Technology, Zhejiang University, n’eddwaliro lya Peking Union Medical College. Enkolagana ng’eyo ey’ebitongole ey’enjawulo eraga obumanyirivu bwe obw’enjawulo mu by’ensoma n’okunoonyereza.
Mu nsonga z’okunoonyereza, Zhang B alina ebika by’amasomo bingi. Obukugu bwe bukwata ku Endocrinology & Metabolism, General & Internal Medicine, Oncology, Cardiovascular System & Cardiology, ne Radiology, Eddagala lya Nuclear & Medical Imaging. Omulimu gwe mu bintu bino gulaga okumanya kwe okw’obwegendereza n’ebintu ebikulu by’akola mu kutumbula ssaayansi w’obusawo n’okutumbula enkola z’ebyobulamu. Zhang B awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [1].
