Research Survodutide Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na Survodutide?
Ikwirakwizwa ry'indwara za metabolike:
Hamwe no kwihuta k'umuvuduko w'ubuzima no guhindura imiterere yimirire, indwara ziterwa na metabolike nkumubyibuho ukabije, diyabete yo mu bwoko bwa 2 mellitus, hamwe na steatohepatite idafite inzoga (NASH) byabaye ikibazo cy’ubuzima rusange ku isi. Kurugero, ubwiyongere bwindwara zumwijima ziterwa na metabolike (MAFLD) zirenga 30%, kandi biteganijwe ko mumwaka wa 2030, imikorere mibi ya metaboloque iterwa na steatohepatitis (MASH) izaba intandaro yo gutera umwijima, bigatera umutwaro munini sisitemu yubuzima.
Imipaka yibiyobyabwenge biriho:
Imiti gakondo ya GLP-1 ifite aho igarukira mu kuvura indwara ziterwa na metabolike. Ku barwayi bamwe, ingaruka zo kugabanya ibiro ntabwo zishimishije, cyangwa barashobora guhura n'ingaruka za gastrointestinal. Byongeye kandi, ubushobozi bwabo bwo kuzamura ibinure byumwijima ni bike, kandi kwihanganira bishobora gutera imbere ukoresheje igihe kirekire.
Ibyiza bya Dual Agoniste:
Nka agonisti ebyiri ya glucagon imeze nka peptide-1 yakira peptide-1 (GLP-1R) hamwe na glucagon reseptor (GCGR), Survodutide irashobora kugenga metabolism kuva mubice byinshi. Binyuze mu nzira ya GLP-1R, irashobora guhagarika ubushake bwo kurya, gutinda gusohora gastric, no guteza imbere insuline kugirango igabanye urugero rwa glucose. Binyuze mu nzira ya GCGR, irashobora kongera aside irike mu mwijima, igabanya ibinure, kandi igateza imbere fibrosis y'umwijima, ikerekana ingaruka nziza zo kuvura umubyibuho ukabije, diyabete, n'indwara z'umwijima mu bushakashatsi bw’inyamaswa.
Nubuhe buryo bwo gukora bwa Survodutide?
1. Kwakira kabiri Agonism
Survodutide ni agoniste ebyiri ya reseptor ya glucagon (GCGR) / glucagon imeze nka peptide-1 (GLP-1R).
GLP-1R Agonism
Nyuma yo gukora reseptor ya GLP-1, irashobora kongera insuline iterwa na glucose kandi ikabuza gusohora glucagon, bityo bikagabanya urugero rwa glucose. Iyo Survovudutide ikora GLP-1R, irashobora guteza imbere gusohora insuline ikorwa na selile pancreatic islet β selile, kandi mugihe kimwe, igabanya imisemburo ya glucagon ikorwa na selile pancreatic islet α selile, ikagenga neza glucose yamaraso [1].
Byongeye kandi, GLP-1R agonism irashobora kandi gutinza ubusa igifu no kongera ibyuzuye, bityo bigafasha kugabanya ibiryo no kugenzura ibiro byumubiri.
GCGR Agonism
Gukora glucagon reseptor birashobora kongera ingufu kandi bigatera amavuta kugabanuka. Survodutide itera GCGR, ikongerera imbaraga umubiri imbaraga za metabolisme kandi bigatuma igabanuka rya triglyceride muri tipusi ya adipose muri aside irike na glycerol, bigatanga umubiri imbaraga [1].
2. Ingaruka kuri Metabolism
Gutezimbere Metabolism ya Glucose
Survovudutide igabanya cyane urwego rwa glycated hemoglobine (HbA1c). Mu bushakashatsi bw’ubuvuzi, abarwayi ba diyabete yo mu bwoko bwa 2 bavuwe na Survovudutide bagaragaje igabanuka rikabije ry’urwego rwa HbA1c nyuma y’ibyumweru 16 bivurwa. Kurugero, ugereranije na semaglutide, dose ya Survovudutide (DG2) yagize ingaruka nkizo mukugabanya HbA1c. Urwego rwa HbA1c mu itsinda rya DG2 rwagabanutseho 15,95 mmol / mol (-1.46%), mu gihe mu itsinda rya semaglutide ryagabanutseho 16.07 mmol / mol (-1.47%) [1].
Uburyo bwibikorwa byabwo bushobora kugerwaho hongerwa imisemburo ya insuline, ikabuza gusohora glucagon, no kunoza gufata no gukoresha glucose nuduce twa periferiya.
Amabwiriza ya Lipid Metabolism
Survovudutide irashobora kugabanya urugero rwa lipide. Mu bushakashatsi bwakozwe ku barwayi bafite umubyibuho ukabije, ugereranije na placebo, Survodutide yagabanije cyane urugero rwa triglyceride (TG), kandi inagabanya urugero rwa lipoprotein nkeya (LDL), cholesterol yuzuye (TC), hamwe na cholesterol ya lipoprotein idafite ubukana bwinshi (non-HDL-C) mu matsinda amwe n'amwe akoreshwa [2].
Muri icyo gihe, Survodutide irashobora kandi kugabanya ibinure byumwijima. Mu bushakashatsi bwakozwe ku barwayi bafite imikorere mibi ya metabolike iterwa na steatohepatitis (MASH), umubare w'abarwayi bavuwe na Survovudutide ibinure by'umwijima byagabanutse byibuze 30% byari hejuru cyane ugereranije no mu itsinda rya placebo. Kurugero, 63%, 67%, na 57% byabarwayi bo mumatsinda ya Survovudutide 2,4mg, 4.8mg, na 6.0mg, bageze kuri iki cyerekezo, mugihe 14% gusa mumatsinda yabobo [3].
3. Ingaruka kuri sisitemu yumutima
Gutezimbere Impanuka Zumutima
Survovudutide irashobora kugabanya umuvuduko wamaraso. Ku barwayi bafite umubyibuho ukabije, ugereranije na placebo, umuvuduko w'amaraso wa sisitemu (SBP) n'umuvuduko w'amaraso wa diastolique (DBP) wagabanutse cyane nyuma yo kuvurwa na Survodutide. Mu buvuzi nyabwo, Survodutide irashobora kugabanya SBP kugera kuri 10.2 mmHg na DBP kuri 4.8 mmHg, kandi ingaruka zo kugabanya umuvuduko wamaraso zirasa utitaye ko umurwayi yari afite hypertension mbere yo kwisuzumisha [2].
Byongeye, Survodutide irashobora kandi kugabanya umuzenguruko. Ku barwayi bafite umubyibuho ukabije, uruziga rw'ikibuno rw'abarwayi bo mu matsinda yose ya Survodutide rwaragabanutse, kandi itsinda rya 4.8mg ryaragabanutse cyane ku kigereranyo cya cm 16,6 ..
Ingaruka kubimenyetso bya Steatohepatitis idafite inzoga (NASH)
Survovudutide irashobora kugira ingaruka nziza kubimenyetso bimwe na bimwe bya steatohepatite idafite inzoga (NASH). Ubushakashatsi bugezweho bwerekana ko Survodutide ishobora kugira uruhare mu kubuza iterambere rya NASH mu kunoza amavuta y’umwijima ndetse no gutwika [4].
Ni ubuhe buryo bukoreshwa na Survodutide?
1. Kuvura Diyabete yo mu bwoko bwa 2 Mellitus n'umubyibuho ukabije
Nkumwanya muremure ukora agoniste, Survodutide itangwa rimwe mubyumweru kandi yerekanye ingaruka zikomeye mukuvura diyabete yo mu bwoko bwa 2 (T2DM) n'umubyibuho ukabije.
Kugabanya Hemoglobine Glycated (HbA1c):
Igeragezwa ryinshi ryamavuriro ryerekanye ko Survodutide ishobora kugabanya neza urwego rwa HbA1c kubarwayi. Kurugero, mubushakashatsi bwakozwe nabarwayi ba T2DM, nyuma yibyumweru 16 bivurwa, urwego rwa HbA1c rwaragabanutse kugera kuri 1.7% [4] . HbA1c ni ikimenyetso cyingenzi kigaragaza igihe kirekire cyo kugenzura amaraso ya glucose, kandi kugabanuka kwayo bivuze ko kugenzura amaraso ya glucose yumurwayi byateye imbere.
Gutakaza Ibiro Bikomeye:
Ku barwayi bafite T2DM n'umubyibuho ukabije, Survodutide irashobora kugabanya ibiro bigera kuri 14.9% mu byumweru 46 byo kwivuza [4] . Iyi ni intambwe ikomeye kubarwayi bahangayikishijwe no kongera ibiro akenshi biterwa n'imiti gakondo ya antidiabete. Kugabanya ibiro ntibifasha gusa kunoza isura yumurwayi nubuzima bwiza ahubwo binagabanya ibyago byingaruka nkindwara zifata umutima.
2. Kunoza ibintu byangiza umutima
Survodutide nayo igira ingaruka nziza kumutima.
Kugabanya umuvuduko w'amaraso:
Mu isuzuma ry’amavuriro y’abarwayi bafite umubyibuho ukabije, ugereranije na placebo, Survodutide irashobora kugabanya umuvuduko wamaraso wa systolike kugera kuri mm2HH 10.2 hamwe n’umuvuduko wamaraso wa diastolique kuri 4,8 mmHg [2] . Kugabanya umuvuduko wamaraso bifite akamaro kanini mukurinda indwara zifata umutima nimiyoboro, cyane cyane kubarwayi bafite umubyibuho ukabije ndetse na hypertension.
Kunoza ibipimo by'amaraso Lipid:
Survodutide irashobora kugabanya urugero rwa triglyceride (TG) kandi ikagira n'ingaruka zimwe na zimwe zigira ingaruka ku bipimo bya lipide yo mu maraso nka lipoproteine yuzuye (HDL), lipoproteine yuzuye (LDL), cholesterol yuzuye (TC), hamwe na cholesterol ya lipoprotein idafite ubukana bwinshi (non-HDL-C) [2] . Kurugero, mubuvuzi buteganijwe, impuzandengo ya TG mumatsinda yose ya Survodutide yagabanutse cyane.
3. Kuvura Steatohepatite idafite inzoga (NASH)
Survodutide yerekana kandi ubushobozi mukuvura steatohepatite idafite inzoga (NASH).
Gutezimbere amateka yumwijima:
Mu byumweru 48, icyiciro cya 2 cyamavuriro y’abarwayi bakuze barwaye MASH (metabolic dysfunction-associated steatohepatitis) na fibrosis yumwijima, Survodutide yarutaga umwanya wa platbo mugutezimbere MASH nta kongera fibrosis yumwijima. By'umwihariko, mu barwayi bavuwe bafite dosiye zitandukanye za Survodutide, 47% by'abarwayi bo mu itsinda rya 2.4mg, 62% by'abarwayi bo mu itsinda rya 4.8mg, na 43% by'abarwayi bo mu itsinda rya 6.0mg bagaragaje ko bateye imbere muri MASH, mu gihe 14% bonyine mu itsinda rya placebo [3].
Kugabanya ibinure byumwijima:
Survodutide irashobora kandi kugabanya ibinure byumwijima. Mu isuzuma ry’amavuriro ryavuzwe haruguru, 63%, 67%, na 57% by’abarwayi bavuwe na 2.4mg, 4.8mg, na 6.0mg ya Survodutide, bagabanutse ku binure by’umwijima byibuze 30%, mu gihe 14% gusa mu itsinda rya placebo [3].
Gutezimbere Fibrosis Yumwijima:
Byongeye kandi, yazamuye fibrosis yumwijima kurwego runaka. Muri uru rubanza, 34%, 36%, na 34% by’abarwayi bavuwe na 2.4mg, 4.8mg, na 6.0mg ya Survodutide, bagaragaje ko hari iterambere ry’imitsi y’umwijima byibuze icyiciro kimwe, mu gihe yari 22% mu itsinda rya placebo [3].
4. Ingaruka kubyo ukunda ibiryo no kunoza Dyslipidemiya
Mubyitegererezo bifite umubyibuho ukabije, Survodutide nundi muti, Semaglutid, urashobora gutera kugabanuka no kugabanya igipimo cyo kurwanya insuline (HOMA-IR), ariko bigira ingaruka zitandukanye kubyo ukunda ibiryo na dyslipidemiya.
Ingaruka ku Kurya Ibiryo:
Semaglutid yagabanije cyane gufata ibiryo bisanzwe nibiryo birimo amavuta menshi mucyumweru cya mbere cyo kuvura ariko nyuma igaruka ku gaciro fatizo. Muri icyo gihe, byongereye cyane gufata amazi asanzwe kandi bigabanya gufata amazi akungahaye kuri fructose. Ibinyuranye na byo, Survodutide ntabwo yahinduye gufata ibiryo bisanzwe n'amazi asanzwe ahubwo byagabanije cyane gufata ibiryo birimo amavuta menshi n'amazi akungahaye kuri fructose mugihe cy'ibyumweru 5 byo kuvura [5].
Ingaruka kuri Lipide Yamaraso:
Semaglutid na Survodutide byombi birashobora kugabanya cyane plasma ya cholesterol yuzuye, hamwe no kugabanuka kwa 24% na 41%. Kugabanuka kurwego rwa cholesterol yose hamwe na Semaglutid byatumye igabanuka rya 25% murwego rwa cholesterol ya lipoprotein nyinshi, ariko urugero rwa cholesterol ya lipoprotein nkeya ntirwahindutse. Ingaruka zo kugabanya cholesterol ya Survodutide yagaragaye mu bice byose bya lipoproteine, harimo no kugabanya 39% bya cholesterol ya lipoprotein nkeya ..
Mu gusoza, nka reseptor ebyiri agonist, Survodutide irashobora kugenga metabolisme, kugabanya glucose yamaraso, kugabanya ibiro byumubiri, kunoza ibintu byangiza umutima nimiyoboro y'amaraso, no kunoza ibimenyetso bya steatohepatite idafite inzoga. Itanga ibitekerezo bishya byo kuvura indwara zifitanye isano kandi bifite akamaro kanini mukuzamura urwego rwubuzima bwabarwayi.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Le Roux C numushakashatsi ufatanije nimiryango myinshi. Muri byo harimo Ishuri Rikuru rya Kaminuza Dublin, St Vincents Uni Hosp, Kaminuza ya Ulster, Ibitaro bya Kaminuza bya Saint Vincent, St Vincents Hosp Grp, KU Leuven, Ibitaro bya Kaminuza Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, Kaminuza ya Gothenburg, Imperial College London, ICL, Univ Dublin, Istituto kuri la Sintesi Organica e la ISO Ibitaro bya King's College, Ibitaro bya King's College NHS Foundation Icyizere, Ibitaro bya Parike ya Musgrove n’ibitaro by’igihugu bya Neurologiya & Neurosurgie.
Inyungu zubushakashatsi bwe ni nini - zirimo, Kubaga, Endocrinology & Metabolism, Imirire & Dietetics, Oncology, na Biochemie & Molecular Biology. Ibikorwa bye muri ibi bice byerekana ubuhanga bwe n’umusanzu ukomeye yagize mu guteza imbere ubumenyi bw’ubuvuzi. Le Roux C yanditse murutonde rwerekana [2].
