Na Cocer Peptides 
ukwezi gushize
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
1. Intangiriro
Umubyibuho ukabije wabaye impungenge z’ubuzima rusange ku isi, byongera cyane ibyago by’ingaruka zitandukanye nk'indwara z'umutima n'imitsi na diyabete. Kubona imiti ivura umubyibuho ukabije ningirakamaro cyane. Survodutide, nka agoniste ebyiri ikora kuri reseptor ya glucagon (GCGR) hamwe na glucagon imeze nka peptide-1 yakira (GLP-1R), yerekana imbaraga nyinshi mubijyanye no kuvura umubyibuho ukabije.
Igicapo 1 Ingaruka za glucagon zisa na peptide-1 (GLP-1), glucose-iterwa na insulineotropique polypeptide (GIP), na glucagon kumubiri ningingo zitandukanye.
2. Incamake ya Survodutide
2.1 Amavu n'amavuko
Kwiyongera ku isi hose umubyibuho ukabije hamwe na diyabete yo mu bwoko bwa 2 (T2DM) bikomeje kwiyongera, kandi imiti gakondo ya antidiabete ikunze gutuma ibiro byiyongera, bigatuma hakenerwa byihutirwa imiti mishya ishobora kuvura icyarimwe T2DM n'umubyibuho ukabije. GLP-1 yakira reseptor agoniste (GLP-1 RAs) hamwe na GLP-1 / GIP reseptor agonist bagaragaje imbaraga mugutakaza ibiro no kunoza metabolike, Survodutide (BI 456906) yagaragaye nkumukandida utanga ikizere, umaze igihe kinini ukora agoniste ukora iperereza.
2.2 Uburyo bukoreshwa
Ibintu bidasanzwe bya Survodutide biri mubushobozi bwayo icyarimwe gukora GCGR na GLP-1R. GCGR igenga cyane cyane glucose yamaraso, igatera glycogenolysis na gluconeogenezi mu mwijima iyo ikora, bityo ikazamura urugero rwa glucose. Muburyo bwibikorwa bya Survodutide, ntabwo izamura gusa glucose yamaraso ahubwo igenga metabolisme yingufu binyuze mubikorwa byo guhuza hamwe na GLP-1R. GLP-1R ikwirakwizwa cyane mu ngingo no mu ngingo nyinshi, harimo pancreas, gastrointestinal tract, umutima, n'ubwonko. Gukora GLP-1R biteza imbere gusohora kwa insuline, bikabuza gusohora glucagon, gutinda gusohora gastrica, kongera guhaga, bityo kugabanya ibiryo no kugabanya ibiro byumubiri. Survodutide igira uruhare runini muguhindura metabolike binyuze muburyo bubiri bwa reseptor agonism, ifasha mukuvura umubyibuho ukabije.
3. Uruhare rwa Survodutide mu kuvura umubyibuho ukabije
3.1 Ingaruka yo Kugenzura Ibiro
Ubushakashatsi bwinshi bw’amavuriro bwerekanye ko Survodutide igira ingaruka zikomeye zo kugabanya ibiro ku barwayi bafite umubyibuho ukabije. Mu cyiciro cya 2 cy’amavuriro yibasiye abantu bafite umubyibuho ukabije badafite diyabete, 387 bitabiriye amahugurwa bafite hagati y’imyaka 18 na 75 bafite icyerekezo rusange cy’umubiri (BMI) kg27 kg / m² bashinzwe kubushake mumatsinda atanu, bakira buri cyumweru inshinge zo munsi ya Survodutide (0,6, 2.4, 3.6, cyangwa 4.8 mg) cyangwa umwanya wa byumweru 46. Nyuma y'ibyumweru 46, amatsinda yose ya Survodutide yerekana ko yagabanutse ibiro, hamwe na 4.8 mg itsinda ryagabanutse ku kigereranyo cya 18.7%. Duhereye ku isesengura ry’itsinda ryakozwe ku gitsina na BMI, abagore bagaragaje ibiro byinshi bagabanutse nyuma yo guhabwa mg 4,8 za Survodutide, ugereranyije ugereranyije ibiro -17.0%, mu gihe abagabo bafite -11.9%. Mu matsinda atandukanye ya BMI, abitabiriye hamwe na BMI <30 kg / m² wakiriye Survodutide 4.8 mg ivura yagize uburambe bwo kugabanuka cyane, agera kuri -19.1%. Ibi byerekana ko Survodutide igira ingaruka zo kugabanya ibiro ku barwayi bafite umubyibuho ukabije w’uburinganire butandukanye ndetse n’urwego rwa BMI, hamwe n’ingaruka zigaragara mu matsinda amwe.
Igishushanyo 2 Iherezo ryibanze nyuma yibyumweru 48 byo kuvura.
3.2 Ingaruka zo Gukwirakwiza Amavuta Yumubiri
Usibye kugabanya ibiro byose, Survodutide yagize n'ingaruka nziza mugukwirakwiza amavuta yumubiri. Ugereranije nitsinda rya placebo, amatsinda yose ya Survodutide yerekana ko yagabanutse kumuzenguruko, hamwe na 4.8 mg itsinda ryagabanutse cyane kuri cm 16,6. Kugabanuka kuzenguruka mu kibuno byerekana kugabanuka kw'amavuta yo munda, bifitanye isano rya bugufi n'indwara z'umutima. Ibi byerekana ko Survodutide itagabanya ibiro byumubiri gusa ahubwo inagabanya ikwirakwizwa ryamavuta yumubiri kugabanya ibinure byo munda, bityo bikagabanya ibyago byindwara ziterwa numubyibuho ukabije.
3.3 Gutezimbere ibipimo bya metabolike
Survodutide ntabwo igenga uburemere bwumubiri gusa ahubwo igira n'ingaruka nziza kubintu byinshi byo guhinduranya. Kubijyanye na metabolisme ya lipide, mugihe cyo kuvura, triglyceride (TG) yagabanutse cyane mumatsinda yose ya Survodutide, kandi lipoprotein nkeya cyane (VLDL) yagabanutseho gato mumatsinda yose ya Survodutide. LDL yagabanutse mu matsinda ya dose ya 2,4 na 3,6 mg, mu gihe cholesterol yose (TC) na cholesterol itari HDL (itari HDL-C) yagabanutse mu matsinda 0,6, 2.4, na 3,6 mg. HDL yagumye ihagaze neza mubuvuzi. Ku bijyanye n'umuvuduko w'amaraso, mu buvuzi nyabwo, Survodutide irashobora kugabanya umuvuduko w'amaraso wa systolike (SBP) kugera kuri 10.2 mmHg hamwe n'umuvuduko w'amaraso wa diastolique (DBP) na 4.8 mmHg, hamwe n'ingaruka nk'izo zigabanya umuvuduko w'amaraso byagaragaye hatitawe ku kuba hypertension yari ihari mbere yo kwisuzumisha. Iterambere ryibipimo bya metabolike rifasha kugabanya ibyago byindwara zifata umutima nimiyoboro yabarwayi bafite umubyibuho ukabije, bikarushaho kwerekana ibyiza bya Survodutide muburyo bwo kuvura umubyibuho ukabije.
3.4 Uburyo bwibikorwa
Survodutide ikora ingaruka zo kugabanya ibiro ukoresheje GCGR na GLP-1R. Gukora GLP-1R bitera gusohora insuline, byongera insuline, bikagabanya ubushake bwo kurya, kandi bikagabanya gufata ibiryo. Iradindiza kandi gusiba gastric, ikongerera igihe ibiryo biguma mu gifu kandi bikarushaho kwiyongera. Gukora kwa GCGR bigira uruhare mugutunganya metabolike ya hepatike iteza imbere okiside yibinure no guhagarika ibinure, bityo bikagabanya ibinure mumubiri. Survodutide irashobora kandi guhindura imbaraga za metabolism hamwe nuburemere bwumubiri binyuze muburyo butaziguye nko kugenzura mikorobe yo munda.
4. Gukoresha Survodutide mukuvura umubyibuho ukabije
4.1 Ibimenyetso byubushakashatsi
Mu bushakashatsi bwakozwe ku barwayi barwaye diyabete yo mu bwoko bwa 2 n'umubyibuho ukabije, Survodutide yerekanye kandi ingaruka nziza za hypoglycemic ndetse no kugabanya ibiro. Nyuma yibyumweru 16 byo kuvurwa, abarwayi ba hemoglobine A1c (HbA1c) bagabanutse cyane, aho byagabanutse cyane 1,7%, kandi uburemere bwumubiri nabwo bwaragabanutse cyane, aho byagabanutse cyane 14.9%. Mu bushakashatsi bwakozwe ku barwayi bafite imikorere mibi ya metabolike iterwa na steatohepatitis (MASH) n'umubyibuho ukabije, Survodutide ntabwo yateje imbere ibimenyetso by’umwijima gusa ahubwo byanatumye abarwayi bagabanuka. Ubu bushakashatsi burashimangira kandi imikorere ya Survodutide mubantu batandukanye bafite ibibazo bijyanye n'umubyibuho ukabije.
4.2 Ibyiza byo kugereranya kurenza ibindi biyobyabwenge
Ugereranije nibiyobyabwenge gakondo bigabanya ibiro, Survodutide itanga ibyiza byinshi. Imiti gakondo igabanya ibiro akenshi yibasira uburyo bumwe, bikavamo imikorere mike kandi ibyago byinshi byingaruka mbi. Survodutide, ikora binyuze muburyo bubiri bwa reseptor agonism, igabanya neza uburemere bwumubiri mugihe icyarimwe itezimbere ibipimo bya metabolike nka glucose yamaraso, urugero rwa lipide, numuvuduko wamaraso, bityo bigatanga gukumira no kuvura byimazeyo ibibazo biterwa numubyibuho ukabije.
Ugereranije nindi miti igabanya ibiro nka semaglutide (GLP-1 reseptor agonist), mubushakashatsi bwibikoko, Survodutide na semaglutide byombi byatumye ibiro bigabanuka. Nyamara, Survodutide yerekanye ingaruka zidasanzwe kubyo ukunda ibiryo na lipide idasanzwe. Semaglutid igabanya gufata ibiryo mugihe cyambere cyo kuvura ariko ikagaruka kurwego rwibanze nyuma, mugihe Survodutide ikomeza kugabanya gufata indyo yuzuye amavuta namazi menshi ya fructose mugihe cyibyumweru 5 byo kuvura. Kubijyanye na profili ya lipide, Semaglutid igabanya cyane cyane cholesterol igabanya HDL-cholesterol, mugihe Survodutide yerekana ko cholesterol igabanuka mubice byose bya lipoproteine, harimo na LDL-cholesterol. Ibi birerekana ko Survodutide ishobora gutanga ingaruka nziza mugutunganya ibiryo hamwe na profili ya lipide.
5. Umwanzuro
Survodutide, nk'igitabo gishya cya agonist ya GCGR / GLP-1R, cyerekana akamaro gakomeye mu kuvura umubyibuho ukabije. Ntabwo igabanya gusa uburemere bwumubiri kandi inatezimbere ikwirakwizwa ryamavuta yumubiri ahubwo inagenga byimazeyo ibipimo byinshi bya metabolike nka glucose yamaraso, lipide yamaraso, numuvuduko wamaraso, bitanga inyungu zinyuranye kubarwayi bafite umubyibuho ukabije.
Inkomoko
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[5] MBU we, Rosenstock J, Hoefler J, n'abandi. Ingaruka - ibisubizo kuri HbA1c no kugabanya ibiro bya survodutide, glucagon ebyiri / GLP-1 reseptor agonist, ugereranije na placebo na label semaglutide kubantu barwaye diyabete yo mu bwoko bwa 2: kwipimisha kwa muganga [J]. Diyabete, 2023,67: 470-482.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
