Semaglutid 5mg

SemaglutidStructure Imiterere ya

Research Ubushakashatsi bwa Semaglutid

Ni ubuhe bushakashatsi bwakozwe na Semaglutid?

Semaglutid ni glucagon yumuntu isa na peptide-1 (GLP-1) analogue, iri mubyiciro byimiti ya GLP-1 reseptor agonist. GLP-1 ni imisemburo isanzwe ibaho isohorwa na selile zo munda nyuma yo kurya, itera gusohora insuline kandi ikabuza gusohora glucagon kugirango igabanye urugero rwa glucose. Iterambere rya Semaglutid ryaturutse ku bushakashatsi bwimbitse ku mikorere ya physiologiya ya GLP-1. GLP-1 ifite ubuzima bucye bwigihe gito mumubiri, nkiminota 1-2, kuko yangirika byoroshye na dipeptidyl peptidase-4 (DPP-4) imisemburo mumubiri. Kugira ngo ibyo bigabanuke, abahanga bahinduye imiterere ya GLP-1, binjiza insimburangingo ya aside amine kandi bongeraho amatsinda yo gukingira kugira ngo barwanye imisemburo ya DPP-4, bityo bongere igihe cyo gukora mu mubiri ^[1] . Mu miterere ya Semaglutid, alanine iri ku mwanya wa 8 isimburwa na α-aminoisobutyric aside (Aib), ntabwo iteza imbere gusa imiti ihamye ahubwo inongerera imbaraga imbaraga zayo hamwe na reseptor ya GLP-1 ^[2] . Urunigi rudasanzwe rwa aside irike yongewe kuri C-terminus ya Semaglutid, ihuza ibisigisigi bya lysine ikoresheje γ-glutamine, bikongerera ubuzima igice cy’ibiyobyabwenge kandi bikemerera guterwa inshuro imwe mu cyumweru cyangwa gufatwa mu kanwa rimwe ku munsi ^[1] . Semaglutid yabanje gukorwa ishingiye ku bushakashatsi no guhindura GLP-1 karemano, igamije gutanga ubuvuzi bunoze ku barwayi bafite metabolism yo mu bwoko bwa 2 ^{[1, 2]} . Binyuze muri ubwo buryo bwiza, Semaglutid ntigumana gusa ibikorwa bya physiologique ya GLP-1 ahubwo inatezimbere cyane imiti ya farumasi, ihinduka GLP-1 yakira reseptor agonist ifite agaciro gakomeye kivuriro. Iterambere rya Semaglutid nigikorwa gikomeye, kizana uburyo bushya bwo kuvura abarwayi bafite metabolism yo mu bwoko bwa 2. Muguhindura imiterere ya GLP-1 karemano, irenga imbogamizi yubuzima bwayo bwigihe gito kandi igateza imbere ibiyobyabwenge nigihe cyo gukora.

Nubuhe buryo bwo gukora bwa Semaglutid?

Semaglutid ni glucagon ikora nka peptide-1 (GLP-1) reseptor agonist, kandi uburyo bwibikorwa byayo bugerwaho ahanini binyuze mubice bikurikira:

Amaraso ya glucose:

Semaglutid nigitabo GLP-1 reseptor agonist (GLP-1RA). Uburyo bwibanze bwayo ni ukurinda irari ryibiryo muguhagarika ubushake bwo kurya, kugabanya ibyifuzo byibiribwa birimo amavuta menshi, no guhindura ikigo cyo kugaburira hypothalamic kugabanya ibiryo. Yongera kandi guhaga, gutinda gusiba gastric, no kugabanya umuvuduko wa gastrointestinal, bityo bikagabanuka. Kugabanya ibiro byongera insuline kandi bigafasha kugabanya urugero rwa glucose yamaraso ^[3] . Semaglutid itera kugabanuka mubibabi binyuze mumihanda ikwirakwizwa. Ubushakashatsi bwerekana ko bukora ku bwonko, septal nucleus, na hypothalamus ariko ntiburenga inzitizi y'amaraso n'ubwonko. Ahubwo, ikorana n'ubwonko binyuze mu ngingo zizenguruka no mu bice byegeranye. Semaglutid ikora c-Fos mu turere icumi twubwonko, harimo uduce twinyuma twibasiwe nu turere twa kabiri nka nucleus ya parabrachial nucleus idafite GLP-1R itaziguye. Isesengura ryikora ryerekana ko gukora birimo parabrachial nucleus neurons igenzura iherezo ryibiryo, bityo bikagenga glucose yamaraso ^[4] .

Gastrointestinal regulation:

Semaglutid ikora kuri reseptor ya GLP-1 munda, ikoresheje inzira ya vagus nervice kugirango ihindure moteri ya gastrointestinal. Irwanya kugabanuka kwa antral, itera pyloric sphincter impagarara, kandi ikongerera kugaburira ibiryo byo mu gifu, gutinda kwinjira munda no kwirinda indwara ya glucose nyuma yamaraso, bigatuma urwego ruhamye ^[5] . Byongeye kandi, Semaglutid igira ingaruka hagati ya GLP-1 yakira, cyane cyane muri hypothalamic arcuate na nuclei paraventricular. Irabuza ibintu bitera ubushake bwo kurya, nka neuropeptide Y (NPY) na poroteyine ifitanye isano na agouti (AgRP), mugihe ikora neurone ya proopiomelanocortin (POMC) kugirango yongere imisemburo ya alpha-melanocyte itera imbaraga (α-MSH ⁾ . Ibi bikorwa bitera guhaga, kugabanya inzara, no kugabanya ibiryo, bifasha gucunga ibiro no kunoza mu buryo butaziguye kugenzura amaraso glucose.

Kurinda umutima n'imitsi:

Semaglutid iteza imbere irekurwa rya aside nitide (OYA) hamwe nizindi vasodilator ziva mu ngirabuzimafatizo ya endoteliyale, bikongera vasodilasiyo n'amaraso. Irabuza kandi gutwika no guhagarika umutima, kugabanya kwangirika kwa endoteliyale hamwe nimpanuka za aterosklerose. Mu kugabanya ubushake bwo kurya no gufata ibiryo, bifasha kugabanya ibiro, kunoza metabolisme ya lipide, kugabanya triglyceride na cholesterol ya lipoprotein nkeya (LDL-C), kandi ikazamura cholesterol ya lipoproteine ​​(HDL-C). Byongeye kandi, birashobora kugirira akamaro umuvuduko wamaraso muguhindura impyiko zimpyiko n imikorere ya neuroendocrine, kugabanya ibyago byumuvuduko ukabije wamaraso no kugabanya ingaruka ziterwa nindwara z'umutima ^. .

Semaglutid na transcriptional amabwiriza ya WAT ​​guhinduranya BAT no gukora BAT.

Inkomoko: Byatangajwe ^[13]

Ubushakashatsi bwingenzi nubushakashatsi

Kubijyanye no gushushanya imiterere yimiti no kuyitezimbere, mugihe cyo gukora semaglutide, hakoreshejwe uburyo bwo guhinduranya bihuza alubumu kugirango hongerwe igihe ibiyobyabwenge. Mu kumenya uburyo bwiza bwo guhuza aside irike hamwe nu muhuza, ubushobozi bwo guhuza albumin bwarushijeho kuba bwiza mugihe hagumijwe gukora neza kuri reseptor ya GLP-1 (GLP-1R) (Knudsen LB, 2019).

Kubijyanye no gukoresha ibiyobyabwenge, semaglutide igira ingaruka nziza zo kugabanya ibiro. Semaglutid ni glucagon isa na peptide-1 yakira reseptor agonist (GLP-1 RA) hamwe no kurandura igice kirekire cyubuzima, ikemerera gutera inshinge buri munsi. Ingaruka yo kugabanya ibiro iratangaje. Ku barwayi bafite metabolism yo mu bwoko bwa 2 (T2DM), gutera inshinge buri cyumweru munsi ya semaglutide bisa nkibyiza mugutakaza ibiro kurusha izindi GLP-1RAs buri cyumweru. Mu cyiciro cya II ikigereranyo cyo gushakisha abarwayi bafite umubyibuho ukabije udafite T2DM, inshuro imwe buri munsi yo gutera insimburangingo ya semaglutide byagize akamaro cyane mu kugabanya ibiro kuruta placebo na rimwe kumunsi 3.0mg liraglutide. Kugabanya ibiro byatewe na semaglutide muri ubu bushakashatsi byarenze igipimo cy’imiti igabanya ubukana bwashyizweho n’ikigo cy’ubuvuzi cy’ibihugu by’Uburayi (EMA) n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), nta kibazo cy’umutekano gifite, byerekana ko inshuro imwe buri munsi yo gutera inshinge munsi ya semaglutide ifite amahirwe yo kuba ibiyobyabwenge bigabanya ibiro ^[7] .

Semaglutid irashobora kunoza imikorere yumutima kandi ikoreshwa mukuvura indwara zifata umutima. Ibyavuye mu igeragezwa rya STEP-HFpEF byatangajwe, aho glucose nyinshi ya antidiabete ya glucagon imeze nka peptide 1 agonist semaglutide yazamuye cyane ibimenyetso byo kunanirwa k'umutima hamwe n'uduce duto duto twa HFpEF kandi bigabanya N-terminal ya B-natriuretic peptide (NT-proBNP). Ubushakashatsi bwagaragaje ingaruka zo kuvura semaglutide ikaze kuri trabeculae yumuntu ku giti cye kandi isanga semaglutide yongereye ubukana bwa trabeculae yo mu bwoko bwa trabeculae inshuro zirenga eshatu muburyo buterwa na dose, bitarinze kongera ubushake bwo kurwara. Izi ngaruka birashoboka cyane kubera kwiyongera kwa sarcoplasmic reticulum Ca2 + gufata. Kuvura cyane semaglutide mu kuvura indwara z'umutima birashobora kunoza imikorere ya atiri bityo bikagabanya ibimenyetso ^[8] .

Semaglutid iri kwigwa kugirango ivurwe na steatohepatite idafite inzoga (NASH). Igishushanyo mbonera cyacyo cyagize uruhare runini mugutezimbere glucose yamaraso, uburemere, umuvuduko wamaraso, lipide, imikorere ya selile, hamwe na sisitemu yumutima nimiyoboro yumutima kubarwayi bafite metabolism yo mu bwoko bwa 2. Byongeye kandi, guteza imbere umunwa wa semaglutide birashobora gutanga inyungu zinyongera kubarwayi muburyo bwo kuvura ^[9] .

Itandukaniro mu gutakaza ibiro Ingaruka za Semaglutid Hafi yabaturage

Ingaruka zo Gutakaza Ibiro Kubantu Bakuze Indwara Yumutima Yumutima, Umubyibuho ukabije cyangwa umubyibuho ukabije nta Metabolism: 

Mu kigeragezo cya SELECT yumutima nimiyoboro y'amaraso, semaglutide yagabanije ibintu bikomeye bibi byumutima nimiyoboro y'amaraso (MACE) ku kigero cya 20% mubantu 17,604 bakuze bafite indwara z'umutima-damura zisanzwe, umubyibuho ukabije cyangwa umubyibuho ukabije, kandi nta metabolisme ^[10] . Muri iri sesengura ryerekanwe mbere, abashakashatsi basuzumye ingaruka za semaglutide ku buremere, ibisubizo bya antropometrike, umutekano, no kwihanganira ibipimo fatizo by’umubiri (BMI). Abarwayi bakira semaglutide bahuye n'ibiro bikabije mu byumweru 65, bikomeza imyaka 4. Mugihe cibyumweru 208, semaglutide yatumye habaho kugabanuka cyane muburemere (-10.2%), kuzenguruka mu kibuno (-7.7 cm), no kugereranya umubyimba-uburebure (-6.9%) ugereranije na placebo (-1.5%, -1,3 cm, na -1.0%; kugereranya kwose byari bifite imibare mibi, amoko yose hamwe nuburinganire, amoko yose hamwe nubwoko butandukanye. ibyabaye. Kuri buri cyiciro cya BMI (<30, 30 kugeza <35, 35 kugeza <40, na ≥40 kg / m²), semaglutide yari ifite igipimo gikomeye cyibintu bibi byabaye (ibyabaye kumyaka 100-imyaka: 43.23, 43.54, 51.07, na 47.06 na 50.48, 49.66, 52.73, hamwe na 60.85 byamanutse kubigeragezo). Mu igeragezwa RITORANYE, semaglutide yatumye ibiro bigabanuka cyane bya clinique ndetse no kunoza antropometrike ugereranije na placebo mu byumweru 208, hamwe no kugabanya ibiro bikomeza imyaka 4.

Ingaruka zo Gutakaza Ibiro Kubyibushye cyangwa Biremereye Abantu badafite Metabolism:  

Isuzuma rifatika ryasuzumye imikorere n'umutekano bya semaglutide ku bantu bafite umubyibuho ukabije cyangwa ufite ibiro byinshi badafite metabolism ^[11] . Iri suzuma ryashushanyije ibisubizo bivuye mu bigeragezo byinshi by’amavuriro, byerekana ingaruka za semaglutide ku kugabanya ibiro, ibipimo bya metabolike, hamwe n’ibisubizo by’ubuzima muri rusange. Ibyavuye mu bushakashatsi byagaragaje ko semaglutide ifitanye isano no kugabanya ibiro no kunoza ibipimo by’ubuzima bijyanye n’umubyibuho ukabije, byerekana ko ishobora kuba uburyo bwiza bwo kuvura abarwayi bafite umubyibuho ukabije. 

Ingaruka zo gutakaza ibiro kubarwayi badafite diyabete (Ibimenyetso biva muri RCT nyinshi): 

Ibigeragezo bine byateganijwe (RCTs) birimo abarwayi bafite uburemere bwibanze bwa kg 96-105 basuzumaga buri cyumweru 2,4 mg munsi ya semaglutide yo munsi yubutaka hiyongereyeho uburyo bwo kubaho (ubujyanama, indyo, imyitozo ngororamubiri) kugirango bagabanye ibiro ^[12] . RCT imwe mu barwayi badafite diyabete (N = 1,961) yatangaje ko igabanuka ry’ibiro 15% (15 kg) na 2% (3 kg) hamwe na placebo nyuma yibyumweru 68 (bifite imibare ikomeye). Umubare w'abarwayi bagera kuri ≥5% guta ibiro ni 86% na 32% (umubare ukenewe mu kuvura [NNT] = 2), naho ≥10% gutakaza ibiro byari 69% na 12% (NNT = 2). Kugabanya ibiro byashyizwe ku byumweru ~ 60. Ibintu bibi bya Gastrointestinal (AEs) byabaye muri 74% na 48% (umubare ukenewe kugirango wangize [NNH] = 3). Guhagarika kubera AEs byari 7% na 3% (NNH = 25). Ibisubizo nkibi byagaragaye muyindi RCT hifashishijwe uburyo bukomeye bwo kubaho (N = 611): semaglutide yateje 16% (17 kg) na 6% (6 kg) kugabanuka. Muri dose-ubushakashatsi RCT ku barwayi badafite diyabete (N = 1,210), buri cyumweru 2,4 mg semaglutide, 1.0 mg semaglutide, cyangwa umwanya wawo watanze bivuze ko ibiro 10%, 7%, na 3% nyuma yibyumweru 68. Ibipimo bigera kuri ≥5% gutakaza ibiro byari 69% (2,4 mg), 57% (1.0 mg), na 29% (umwanya). Kuri 2,4 mg na 1.0 mg, NNT = 9. Umwirondoro wa AE wasaga na dosiye. Mu kubungabunga ibiro RCT (N = 803), abitabiriye badafite diyabete bakiriye semaglutide ya mg 2,4 buri cyumweru mu byumweru 20, hanyuma bahitamo gukomeza semaglutide cyangwa guhindukira kuri placebo. Nyuma yibyumweru 48, abakoresha semaglutide bakomeje gutakaza 8% nabakoresha umwanya wa 7%. 

Muncamake, semaglutide ni GLP-1 reseptor agonist hamwe na progaramu ya progaramu nyinshi. Mu kuvura metabolism, ihuza reseptor ya GLP-1 kugirango iteze imbere gusohora insuline no kubuza irekurwa rya glucagon, igenzura neza urugero rwa glucose yamaraso kandi igatanga uburyo bukomeye bwo kuvura abarwayi bafite metabolism yo mu bwoko bwa 2. Mu rwego rwo kuvura umubyibuho ukabije, semaglutide irashobora kugabanya cyane gufata ingufu binyuze mu buryo nko guhagarika ubushake bwo kurya no gutinda gusohora gastrica, gufasha abarwayi bafite umubyibuho ukabije guta ibiro no kuzamura imiterere yabo. Byongeye kandi, semaglutide yerekana amahirwe yo gukoreshwa mugukumira no kuvura indwara zifata umutima, no kunoza ibintu bishobora gutera indwara z'umutima n'imitsi bitanga uburyo bushya bwo kugabanya indwara ziterwa n'umutima. Kugaragara kwa semaglutide ntabwo bikungahaza uburyo bwo kuvura indwara zifitanye isano gusa ahubwo binazana ibyiringiro bishya byo kuzamura imibereho y’abarwayi n’ubuzima.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Hegner P ni umushakashatsi muri kaminuza ya Regensburg. Ibikorwa bye bikubiyemo Chimie, Sisitemu Yumutima, na Cardiology. Muri Chimie, akora ubushakashatsi bujyanye nubuzima bwumutima. Mu bushakashatsi bwimikorere yumutima, asuzuma imikorere yumutima nimiyoboro, ashakisha ubushishozi bwo kuvura. Ubushakashatsi bwe bw'umutima bwibanze ku kwirinda indwara z'umutima, gusuzuma, no kuvura.

Umusanzu wa Hegner urakomeye. Ubushishozi bwe bwimiti bwatumye imiti mishya yumutima itera. Ibikorwa bye kumikorere yumutima nubwato byongereye gusobanukirwa indwara zifata umutima. Mubuvuzi, ubushakashatsi bwe bwateje imbere imicungire yindwara z'umutima, bizamura ibipimo byita ku barwayi. Muri rusange, uburyo bwa Hegner butandukanye butandukanye butungisha imiti yumutima nimiyoboro y'amaraso, bitanga ibyiringiro byo kugabanya imitwaro yindwara nibisubizo byiza byabarwayi. Hegner P yanditse murutonde rwibisobanuro [8].

Imirongo ijyanye

[1] Memon A, Tehrim M, Kumari B. Semaglutid: umuseke mushya kubarwayi ba diyabete [J]. Ikinyamakuru cy’ishyirahamwe ry’ubuvuzi muri Pakisitani, 2023.73 (3): 721.DOI: 10.47391 / JPMA.7558.

[2] Ma H, Huang W, Wang X, n'abandi. Ubushishozi bwubaka mubikorwa bya GLP-1R na molekile ntoya ya agoniste [J]. Ubushakashatsi bwakagari, 2020,30 (12): 1140-1142.DOI: 10.1038 / s41422-020-0384-8.

[3] Kim HS, Jung C H. Umunwa Semaglutid, Glucagon Yambere Yingirakamaro nka Peptide-1 yakira Agonist: Byaba Isasu ryubumaji kubwoko bwa 2 Metabolism? [J]. Ikinyamakuru mpuzamahanga cya siyansi yubumenyi, 2021,22 (18) .DOI: 10.3390 / ijms22189936.

[4] Gabery S, Salinas CG, Paulsen SJ, n'abandi. Semaglutid igabanya uburemere bwumubiri mu nzoka ikoresheje inzira zagabanijwe [J]. Ubushishozi bwa Jci, 2020,5 (6) .DOI: 10.1172 / jci.ubushishozi.133429.

] Ikinyamakuru cyiperereza rya Metabolism, 2016,7: 64-69.DOI: 10.1111 / jdi.12464.

[6] Ryan DH, Lingvay I, Colhoun HM, n'abandi. Ingaruka za Semaglutid ku ngaruka z'umutima n'imitsi ku bantu bafite umubyibuho ukabije cyangwa umubyibuho ukabije (SELECT) gushyira mu gaciro no gushushanya [J]. Ikinyamakuru Umutima w'Abanyamerika, 2020,229: 61-69.DOI: 10.1016 / j.ahj.2020.07.008.

[7] Christou GA, Katsiki N, Blundell J, n'abandi. Semaglutid nk'umuti urwanya antiobesity [J]. Isuzuma ry'umubyibuho ukabije, 2019,20 (6): 805-815.DOI: 10.1111 / obr.12839.

[8] Hegner P, Seitz S, Schopka S, n'abandi. Semaglutid itezimbere imikorere yamasezerano muri atrium yumuntu [J]. Ikinyamakuru Umutima wiburayi, 2024,45.DOI: 10.1093 / eurheartj / ehae666.3729.

[9] Knudsen LB, Lau J. Ivumburwa n'iterambere rya Liraglutide na Semaglutid [J]. Imipaka muri Endocrinology, 2019,10.DOI: 10.3389 / fendo.2019.00155.

[10] Ryan DH, Lingvay I, Deanfield J, n'abandi. Ingaruka ndende zo kugabanya ibiro bya semaglutide mubyibushye nta metabolisme mugeragezwa RATORANYE [J]. Ubuvuzi bwa Kamere, 2024,30 (7): 2049-2057.DOI: 10.1038 / s41591-024-02996-7.

[11] Alanazi M, Alshahrani JA, Aljaberi AS, n'abandi. Ingaruka za Semaglutid ku bantu bafite umubyibuho ukabije cyangwa umubyibuho ukabije nta Metabolism [J]. Ikinyamakuru Cureus cyubuvuzi, 2024,16 (8) .DOI: 10.7759 / cureus.67889.

[12] Ojeniran M, Dube B, Paige A, n'abandi. Semaglutid yo kugabanya ibiro [J]. Umuganga wumuryango wumunyakanada, 2021,67 (11): 842.DOI: 10.46747 / cfp.6711842.

[13] Papakonstantinou I, Tsioufis K, Katsi V. Ibitekerezo kuri Mechanism of Action ya Semaglutid [J]. Ibibazo biriho muri Biologiya ya Molecular, 2024,46 (12): 14514-14541.DOI: 10.3390 / cimb46120872.

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.