Bya Cocer Peptides 
omwezi gumu emabega
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.
1. Enyanjula
Omugejjo gufuuse ekintu ekyeraliikiriza ebyobulamu by’abantu mu nsi yonna, nga kyongera nnyo obulabe bw’ebizibu eby’enjawulo ng’endwadde z’emisuwa n’emisuwa ne ssukaali. Okuzuula eddagala erikola obulungi erijjanjaba omugejjo kikulu nnyo. Survodutide, nga dual agonist ekola ku glucagon receptor (GCGR) ne glucagon-like peptide-1 receptor (GLP-1R), eraga obusobozi bungi mu kisaawe ky’okujjanjaba omugejjo.
Ekifaananyi 1 Ebikosa glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ne glucagon ku bitundu by’omubiri eby’enjawulo ebikulu n’ebitundu by’omubiri.
2. Okulaba ebikwata ku Survodutide
2.1 Ensibuko y’enkulaakulana
Omuwendo gw’omugejjo n’obulwadde bwa sukaali obw’ekika eky’okubiri (T2DM) mu nsi yonna gweyongera, era eddagala ery’ekinnansi eritta ssukaali litera okuvaako okugejja, ekivaako obwetaavu obw’amangu obw’obujjanjabi obupya obuyinza okujjanjaba T2DM n’omugejjo mu kiseera kye kimu. GLP-1 receptor agonists (GLP-1 RAs) ne dual GLP-1/GIP receptor agonists ziraga nti zikola bulungi mu kugejja n’okulongoosa mu nkyukakyuka y’emmere, Survodutide (BI 456906) evuddeyo ng’esuubiza, dual agonist ekola ebbanga eddene mu kiseera kino eri mu kunoonyereza.
2.2 Enkola y’Ekigendererwa
Ekintu eky’enjawulo ekya Survodutide kiri mu busobozi bwayo okukola GCGR ne GLP-1R omulundi gumu. GCGR okusinga etereeza emiwendo gya glucose mu musaayi, okutumbula glycogenolysis ne gluconeogenesis mu kibumba nga ekoleddwa, bwe kityo n’esitula emiwendo gya glucose mu musaayi. Mu nkola y’okukola kwa Survodutide, tekoma ku kulinnyisa miwendo gya glucose mu musaayi wabula mu kifo ky’ekyo etereeza enkyukakyuka y’amasoboza okuyita mu kukolagana ne GLP-1R. GLP-1R esaasaanidde nnyo mu bitundu n’ebitundu by’omubiri ebingi, omuli olubuto, olubuto, omutima n’obwongo. Okukola GLP-1R kitumbula okufulumya insulini, kiziyiza okufulumya glucagon, kilwawo okufulumya amazzi mu lubuto, kyongera okukkuta, bwe kityo ne kikendeeza ku mmere gy’olya n’okukendeeza ku buzito bw’omubiri. Survodutide ekola ekikolwa ekisingawo ekijjuvu eky’okulungamya enkyukakyuka mu mubiri okuyita mu dual receptor gonism, okuyamba mu kujjanjaba omugejjo.
3. Omulimu gwa Survodutide mu kujjanjaba omugejjo
3.1 Enkola y’okulungamya obuzito
Okunoonyereza okungi kulaga nti Survodutide erina kinene okukendeeza ku buzito mu balwadde abagejjulukuka. Mu kugezesebwa okw’omutendera ogw’okubiri okwagenderera abantu abagejjulukuka abatalina ssukaali, abeetabye mu kugezesebwa 387 ab’emyaka 18 okutuuka ku 75 nga balina body mass index (BMI) ≥27 kg/m² zaagabibwa mu bibinja bitaano mu ngeri ey’ekifuulannenge, nga buli wiiki bafuna empiso za Survodutide (0.6, 2.4, 3.6, oba 4.8 mg) oba placebo wansi w’olususu okumala wiiki 46. Ku nkomerero ya wiiki 46, ebibinja byonna ebya dose ya Survodutide byalaga okugejja, ng’ekibinja kya 4.8 mg kyatuuka ku kukendeera kw’obuzito bwa wakati okutuuka ku bitundu 18.7%. Okusinziira ku kwekenneenya kw’ekibinja ekitono okusinziira ku kikula ky’omuntu ne BMI, abakyala baalaga okugejja okusinga okulabika oluvannyuma lw’okufuna 4.8 mg za Survodutide, nga wakati w’okugejja kwa -17.0%, ate abasajja baali -11.9%. Mu bibinja bya BMI eby’enjawulo, abeetabye mu kugezesebwa nga balina BMI < 30 kg/m² eyafuna obujjanjabi bwa Survodutide 4.8 mg be basinga okugejja, ne batuuka ku -19.1%. Kino kiraga nti Survodutide erina ekikolwa ekikendeeza ku buzito ku balwadde abagejjulukuka ab’ekikula eky’enjawulo n’emitendera gya BMI, ng’ekola nnyo mu bibinja ebimu.
Ekifaananyi 2 Ensonga Enkomerero Enkulu oluvannyuma lwa Wiiki 48 ez’Obujjanjabi Obutegekeddwa.
3.2 Ebikosa Ensaasaanya y’amasavu mu mubiri
Ng’oggyeeko okugejja kwonna, Survodutide era yalina emigaso ku kugabanya amasavu mu mubiri. Bw’ogeraageranya n’ekibinja kya placebo, ebibinja byonna ebya dose ya Survodutide byalaga okukendeera mu kwetooloola ekiwato, ng’ekibinja kya 4.8 mg kyatuuka ku kukendeera okusinga obunene okwa wakati okwa sentimita 16.6. Okukendeera kw’obuwanvu bw’ekiwato kiraga nti amasavu mu lubuto gakendedde, ekikwatagana ennyo n’obulabe bw’obulwadde bw’emisuwa. Kino kiraga nti Survodutide tekoma ku kukendeeza ku buzito bw’omubiri wabula era eyamba n’ensaasaanya y’amasavu mu mubiri ng’ekendeeza ku masavu mu lubuto, bwe kityo n’akendeeza ku bulabe bw’endwadde z’emisuwa ezeekuusa ku mugejjo.
3.3 Okulongoosa mu bipimo by’enkyukakyuka y’emmere
Survodutide tekoma ku kutereeza buzito bwa mubiri wabula era erina ebirungi ku bipimo by’enkyukakyuka y’emmere ebingi. Mu nsonga z’okukyusakyusa amasavu, mu kiseera ky’obujjanjabi, triglycerides (TG) zakendeera nnyo mu bibinja byonna ebya Survodutide, ate very low-density lipoprotein (VLDL) yakendeera katono mu bibinja byonna ebya Survodutide dose. LDL yakendeera mu bibinja bya ddoozi ya 2.4 ne 3.6 mg, ate kolesterol yenna (TC) ne kolesterol atali HDL (non-HDL-C) yakendeera mu bibinja ebya 0.6, 2.4, ne 3.6 mg. HDL yasigala nga tekyukakyuka mu kiseera kyonna eky’obujjanjabi. Ku bikwata ku puleesa, mu bujjanjabi obwennyini, Survodutide esobola okukendeeza puleesa y’omusaayi (SBP) okutuuka ku mmHg 10.2 ne puleesa y’omusaayi (DBP) mmHg 4.8, ng’ebikolwa ebifaanagana eby’okukendeeza puleesa byeyolekera awatali kulowooza oba puleesa yaliwo nga tebannaba kwekebejjebwa. Ennongoosereza zino mu nkyukakyuka y’emmere eyamba okukendeeza ku bulabe bw’endwadde z’emisuwa mu balwadde abagejjulukuka, okwongera okulaga ebirungi bya Survodutide ebijjuvu mu kujjanjaba omugejjo.
3.4 Enkola y’Ekikolwa
Survodutide ekola ebikolwa byayo eby’okugejja ng’ekola GCGR ne GLP-1R. Okukola GLP-1R kitumbula okufulumya insulini, kyongera okuwulira insulini, kiziyiza okwagala okulya, era kikendeeza ku mmere gy’olya. Era kilwawo okufulumya amazzi mu lubuto, ne kiwangaaza ekiseera emmere gy’emala mu lubuto n’okwongera okwongera okukkuta. Okukola kwa GCGR kwetaba mu kulungamya enkyukakyuka y’ekibumba nga kitumbula oxidation y’amasavu n’okuziyiza okukola amasavu, bwe kityo ne kikendeeza okukuŋŋaanyizibwa kw’amasavu mu mubiri. Survodutide era eyinza okukwata ku nkyukakyuka y’amasoboza n’obuzito bw’omubiri okuyita mu nkola ezitali butereevu nga okulungamya obuwuka obutonotono obw’omu byenda.
4. Okukozesa eddagala lya Survodutide mu kujjanjaba omugejjo
4.1 Obujulizi bw’okunoonyereza ku bujjanjabi
Mu kunoonyereza okwakolebwa ku balwadde ba sukaali ow’ekika eky’okubiri n’omugejjo, Survodutide era yalaga nti ekola bulungi ku kukendeeza sukaali n’okugejja. Oluvannyuma lwa wiiki 16 nga bajjanjabiddwa, emiwendo gya hemoglobin A1c (HbA1c) mu balwadde gyakendeera nnyo, nga omuwendo ogusinga obunene gwakendeera ebitundu 1.7%, ate n’obuzito bw’omubiri nagwo bwakendeera nnyo, nga omuwendo ogusinga obunene gwakendeera ebitundu 14.9%. Mu kunoonyereza okwakolebwa ku balwadde abalina obulwadde bwa metabolic dysfunction-associated steatohepatitis (MASH) n’omugejjo, Survodutide teyakoma ku kulongoosa bubonero bwa kibumba mu bitundu by’omubiri wabula yaleeta n’okugejja mu balwadde. Okunoonyereza kuno kwongera okukakasa obulungi bwa Survodutide mu bantu ab’enjawulo abalina embeera ezeekuusa ku mugejjo.
4.2 Enkizo mu kugeraageranya ku ddagala eddala
Bw’ogeraageranya n’eddagala ery’ekinnansi erikendeeza ku mugejjo, Survodutide erimu ebirungi bingi. Eddagala ery’ekinnansi erikendeeza ku mugejjo litera okutunuulira enkola emu, ekivaamu okukola ekitono n’obulabe obw’amaanyi obw’okukosebwa. Survodutide, wabula, ekola okuyita mu dual receptor gonism, ekendeeza bulungi ku buzito bw’omubiri ate mu kiseera kye kimu n’elongoosa mu nkyukakyuka y’emmere nga glucose mu musaayi, emiwendo gy’amasavu, ne puleesa, bwe kityo n’ewa okuziyiza n’okujjanjaba okujjuvu ku bizibu ebiva ku mugejjo.
Bw’ogeraageranya n’eddagala eddala eppya erikendeeza ku buzito nga semaglutide (a GLP-1 receptor agonist), mu kugezesa ebisolo, Survodutide ne semaglutide zombi zaaleeta okugejja. Wabula Survodutide yalaga ebikosa eby’enjawulo ennyo ku mmere gye yeegomba n’obutabeera bulungi mu masavu. Semaglutid ekendeeza ku mmere gye balya mu mitendera egy’okusooka egy’obujjanjabi naye n’edda ku mitendera egyasooka oluvannyuma, ate Survodutide ekendeeza buli kiseera okulya emmere erimu amasavu amangi n’amazzi aga fructose mu bbanga lya wiiki 5 ez’obujjanjabi. Ku bikwata ku bifaananyi by’amasavu, Semaglutid okusinga ekendeeza ku kolesterol yenna ng’ekendeeza ku HDL-cholesterol, ate Survodutide eraga okukendeeza ku kolesterol mu bitundu byonna ebya lipoprotein, omuli ne LDL-cholesterol. Kino kiraga nti Survodutide eyinza okuwa ebikolwa eby’oku ntikko mu kulungamya emmere gye balya n’ebifaananyi by’amasavu.
5. Okumaliriza
Survodutide, nga novel dual agonist of GCGR/GLP-1R, eraga obulungi obw’amaanyi mu kujjanjaba omugejjo. Tekoma ku kukendeeza bulungi ku buzito bw’omubiri n’okulongoosa ensaasaanya y’amasavu mu mubiri wabula era etereeza mu bujjuvu ebipimo by’enkyukakyuka y’emmere ebingi nga glucose mu musaayi, amasavu mu musaayi, ne puleesa, nga kiwa emigaso egy’enjawulo eri abalwadde abagejjulukuka.
Ensonda
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[2] Le Roux CW, Steen O, Lucas K. J., n’abalala. 6926 Okwekenenya ebibinja ebitonotono okusinziira ku kikula ky’omuntu n’omuwendo gw’omubiri (BMI) mu bantu ababeera n’omugejjo/omugejjo mu Survodutide, a Glucagon/GLP-1 Receptor Dual Agonist, Phase II Trial[J]. Journal of the Endocrine Society, 2024,8 (Supplement_1): bvae133-bvae163.DOI: 10.1210 / jendso / bvae163.033.
[3] Sanyal A. J., Bedossa P., Fraessdorf M., n’abalala. Omutendera 2 Randomized Okugezesebwa kwa Survodutide mu MASH ne Fibrosis.[J]. Ekitabo ky’obusawo ekya New England, 2024.
[4] Briand F, Augustin R, Bleymehl K, n’abalala. 7279 Survodutide ne Semaglutid Zombi Zireetera Okugejja naye Ziraga Ebikosa Eby’enjawulo ku Emmere Okwettanira n’Okukendeera kw’Amasavu mu Free Choice Diet-induced Obese Hamster Model[J]. Journal of the Endocrine Society, 2024,8 (Supplement_1): bvae134-bvae163.DOI: 10.1210 / jendso / bvae163.034.
[5] Her MBU, Rosenstock J, Hoefler J, n’abalala. Dose–response effects ku HbA1c n’okukendeeza ku buzito bw’omubiri ku survodutide, dual glucagon/GLP-1 receptor agonist, bw’ogeraageranya ne placebo ne open-label semaglutide mu bantu abalina sukaali ow’ekika eky’okubiri: okugezesebwa okw’obujjanjabi okutali kwa bulijjo[J]. Obulwadde bwa sukaali, 2023,67:470-482.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
