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1 kits (10 Vials)
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▎ Tsarin Semaglutid
Source: PubChem |
Jerin: His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-lys (Aeea-Aeea-γ-glu-octadecanedioic)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH Tsarin kwayoyin halitta: C 187H 291N 45O59 Nauyin Kwayoyin: 4114 g/mol Lambar CAS: 910463-68-2 Lambar CID: 56843331 Ma'ana: Rybelsus; Ozempic; Wegovy |
▎ Binciken Semaglutid
Menene asalin bincike na Semaglutid?
Semaglutid analog ne na ɗan adam glucagon-kamar peptide-1 (GLP-1), wanda ke cikin nau'in magungunan GLP-1 mai karɓar agonist. GLP-1 wani hormone ne da ke faruwa ta dabi'a wanda ƙwayoyin hanji ke ɓoye bayan cin abinci, wanda ke haɓaka ƙwayar insulin kuma yana hana ƙwayar glucagon don daidaita matakan glucose na jini. Ci gaban Semaglutid ya samo asali ne daga bincike mai zurfi game da ayyukan ilimin lissafi na GLP-1. GLP-1 yana da ɗan gajeren rabin rayuwa a cikin jiki, kimanin minti 1-2, saboda yana da sauƙin lalacewa ta hanyar dipeptidyl peptidase-4 (DPP-4) enzymes a cikin jiki. Don shawo kan wannan ƙayyadaddun, masana kimiyya sun gyara tsarin GLP-1, suna gabatar da wasu sauye-sauye na amino acid da kuma ƙara ƙungiyoyi masu kariya don haɓaka juriya ga enzymes DPP-4, ta haka ne ya tsawaita tsawon lokacin aiki a cikin jiki [1] . A cikin tsarin Semaglutid, alanine a matsayi na 8 an maye gurbinsa da α-aminoisobutyric acid (Aib), wanda ba kawai inganta kwanciyar hankali na miyagun ƙwayoyi ba amma yana haɓaka ƙarfin ɗaure tare da masu karɓa na GLP-1 [2] . Ana ƙara sarkar fatty acid na musamman a cikin C-terminus na Semaglutid, wanda aka haɗa da ragowar lysine ta hanyar γ-glutamine, yana kara tsawaita rabin rayuwar miyagun ƙwayoyi kuma yana ba da damar yin allurar sau ɗaya a mako ko kuma a sha da baki sau ɗaya a rana [1] . An fara haɓaka Semaglutid bisa ga bincike da gyare-gyare na GLP-1 na halitta, da nufin samar da magani mafi mahimmanci ga marasa lafiya da nau'in 2 metabolism [1,2] . Ta hanyar waɗannan haɓakawa na tsarin, Semaglutid ba wai kawai yana riƙe da ayyukan ilimin lissafin jiki na GLP-1 ba amma kuma yana inganta haɓakar kayan aikin sa na pharmacokinetic, ya zama agonist mai karɓa na GLP-1 mai tsayi mai mahimmanci na asibiti. Ci gaban Semaglutid babban nasara ne, yana kawo sabbin zaɓuɓɓukan magani ga marasa lafiya da nau'in 2 na metabolism. Ta hanyar haɓaka tsarin GLP-1 na halitta, yana shawo kan ƙayyadaddun gajeriyar rabin rayuwar sa kuma yana haɓaka kwanciyar hankali na miyagun ƙwayoyi da tsawon lokacin aiki.
Menene tsarin aikin Semaglutid?
Semaglutid wani agonist mai karɓa ne na glucagon-kamar peptide-1 (GLP-1), kuma ana samun tsarin aikinsa ta hanyar abubuwa masu zuwa:
Tsarin glucose na jini:
Semaglutid wani labari ne na GLP-1 agonist mai karɓa (GLP-1RA). Tsarinsa na farko shine don hana sha'awar abinci ta hanyar hana ci, rage fifikon abinci mai kitse, da daidaita cibiyar ciyar da hypothalamic don rage cin abinci. Har ila yau, yana ƙara yawan gamsuwa, yana jinkirta zubar da ciki, da kuma rage motsi na gastrointestinal, ta hanyar samun asarar nauyi. Wannan raguwar nauyin nauyi yana haɓaka haɓakar insulin kuma yana taimakawa daidaita matakan glucose na jini [3] . Semaglutid yana haifar da asarar nauyi a cikin rodents ta hanyar rarraba hanyoyin jijiyoyi. Nazarin ya nuna cewa yana aiki akan tushen kwakwalwa, septal nucleus, da hypothalamus amma baya ketare shingen kwakwalwar jini. Maimakon haka, yana hulɗa da kwakwalwa ta hanyar gabobin dawakai da wuraren ventricular-proximal. Semaglutid yana kunna c-Fos a cikin yankuna goma na kwakwalwa, gami da yankunan hindbrain da aka yi niyya kai tsaye da kuma yankuna na biyu kamar tsakiyar tsakiya na parabrachial ba tare da hulɗar GLP-1R kai tsaye ba. Nazari ta atomatik yana ba da shawarar kunnawa ya haɗa da ƙananan ƙwayoyin cuta na parabrachial neurons masu sarrafa ƙarshen abinci, don haka daidaita glucose na jini [4] .
Ka'idojin Gastrointestinal:
Semaglutid yana aiki akan masu karɓar GLP-1 a cikin gut, ta yin amfani da hanyar jijiyar vagus don daidaita motsin ciki. Yana hana ƙayyadaddun antral, yana ƙarfafa tashin hankali na pyloric sphincter, kuma yana tsawaita riƙe abinci na ciki, jinkirta shigarwar duodenal da kuma hana spikes na glucose na jini na baya-bayan nan, yana haifar da ƙarin kwanciyar hankali [5] . Bugu da ƙari, Semaglutid yana rinjayar masu karɓar GLP-1 na tsakiya, musamman a cikin arcuate hypothalamic da paraventricular nuclei. Yana hana abubuwa masu motsa jiki kamar neuropeptide Y (NPY) da furotin da ke da alaka da agouti (AgRP), yayin da yake kunna proopiomelanocortin (POMC) neurons don haɓaka alpha-melanocyte-stimulating hormone (α-MSH) ɓoye [5] . Wadannan ayyuka suna haifar da gamsuwa, rage yunwa, da rage cin abinci, suna taimakawa sarrafa nauyi da inganta sarrafa glucose na jini a kaikaice.
Kariyar zuciya:
Semaglutid yana haɓaka sakin nitric oxide (NO) da sauran vasodilator daga sel endothelial na jijiyoyin bugun jini, haɓaka vasodilation da kwararar jini. Hakanan yana hana kumburi da damuwa na oxidative, rage lalacewar endothelial da haɗarin atherosclerosis. Ta hanyar hana ci da cin abinci, yana taimakawa rage nauyi, yana inganta metabolism na lipid, yana rage triglycerides da low-density lipoprotein cholesterol (LDL-C), kuma yana haɓaka babban adadin lipoprotein cholesterol (HDL-C). Haka kuma, yana iya amfana da hawan jini ta hanyar daidaita hemodynamics na renal da aikin neuroendocrine, rage haɗarin hauhawar jini da rage haɗarin cututtukan cututtukan zuciya [6] .
Semaglutid da ka'idojin rubutu na WAT zuwa fassarar BAT da kunna BAT.
Source: PubMed [13]
Mabuɗin gwaji da bincike
Dangane da ƙirar tsarin sinadarai da haɓakawa, yayin ƙirar semaglutide, an karɓi hanyar da za a iya jujjuyawa ga albumin don tsawaita lokacin aikin maganin. Ta hanyar ƙayyadaddun ingantacciyar haɗuwar fatty acids da masu haɗin gwiwa, an haɓaka ƙarfin ɗaurin albumin yayin da yake kiyaye inganci akan mai karɓar GLP-1 (GLP-1R) (Knudsen LB, 2019).
Dangane da aikace-aikacen miyagun ƙwayoyi, semaglutide yana da tasirin asarar nauyi. Semaglutid shine glucagon-kamar peptide-1 agonist mai karɓa (GLP-1 RA) tare da dogon kawar da rabin rayuwa, yana barin allurar subcutaneous mako-mako. Sakamakon asarar nauyi yana da ban mamaki. A cikin marasa lafiya tare da nau'in 2 metabolism (T2DM), allurar subcutaneous na sati-sati na semaglutide yana da alama ya fi tasiri don asarar nauyi fiye da sauran GLP-1RAs na mako-mako. A cikin gwajin neman kashi na II na kashi na biyu don marasa lafiya masu kiba ba tare da T2DM ba, allurar subcutaneous na semaglutide sau ɗaya a rana ya fi tasiri don asarar nauyi fiye da placebo kuma sau ɗaya a rana 3.0mg liraglutide. Rashin nauyi da semaglutide ya haifar a cikin wannan binciken ya wuce daidaitattun magungunan rigakafin kiba da Hukumar Kula da Magunguna ta Turai (EMA) da Hukumar Kula da Abinci da Magunguna ta Amurka (FDA) suka kafa, ba tare da lamuran aminci ba, yana nuna cewa allurar semaglutide sau ɗaya a rana tana da yuwuwar zama maganin asarar nauyi a nan gaba [7] .
Semaglutid na iya inganta aikin zuciya kuma ana amfani dashi don maganin cututtukan zuciya. An sanar da sakamakon gwajin STEP-HFpEF, wanda babban adadin antidiabetic glucagon-kamar peptide 1 agonist semaglutide ya inganta alamun cututtukan zuciya tare da juzu'in fitarwa (HFpEF) da aka rage N-terminal pro-B-type natriuretic peptide (NT-proBNP) matakan. The study tested the effect of acute semaglutide treatment on isolated human right atrial trabeculae and found that semaglutide increased the tension of human atrial trabeculae by more than three times in a dose-dependent manner, without increasing the tendency for arrhythmias. Wannan tasirin yana da yuwuwa saboda karuwar sarcoplasmic reticulum Ca2+. Maganin semaglutide mai girma a cikin marasa lafiya marasa lafiya na iya inganta aikin atrial kuma don haka rage alamun bayyanar cututtuka [8] .
Ana nazarin Semaglutid don maganin steatohepatitis maras giya (NASH). Tsarinsa na ma'ana ya ba da gudummawa mai yawa don inganta sarrafa glucose na jini, nauyi, hawan jini, lipids, aikin β-cell, da tsarin zuciya da jijiyoyin jini a cikin marasa lafiya da nau'in 2 na metabolism. Haka kuma, haɓakar nau'in nau'in ƙwayar cuta na semaglutide na iya ba da ƙarin fa'idodi ga marasa lafiya dangane da yarda da jiyya [9] .
Bambance-bambance a cikin Tasirin Rage Nauyi na Semaglutid Gabaɗayan Yawan Jama'a
Tasirin Rage Nauyi A cikin Manya masu Ciwon Zuciya, Kiba ko Kiba ba tare da Metabolism ba:
A cikin SELECT sakamakon sakamakon cututtukan zuciya, semaglutide ya rage manyan abubuwan da ke faruwa na zuciya da jijiyoyin jini (MACE) da 20% a cikin manya na 17,604 tare da cututtukan zuciya na zuciya, kiba ko kiba, kuma babu metabolism [10] . A cikin wannan ƙayyadaddun ƙayyadaddun ƙayyadaddun bayanai, masu bincike sunyi nazarin tasirin semaglutide akan nauyi, sakamakon anthropometric, aminci, da juriya ta hanyar ma'aunin jiki na asali (BMI). Marasa lafiya da ke karɓar semaglutide sun sami ci gaba da asarar nauyi sama da makonni 65, suna dagewa har zuwa shekaru 4. A cikin makonni 208, semaglutide ya haifar da raguwar ma'ana mai mahimmanci a cikin nauyi (-10.2%), kewayen kugu (-7.7 cm), da ƙugiya-zuwa tsayi (-6.9%) idan aka kwatanta da placebo (-1.5%, -1.3 cm, da -1.0%, bi da bi; duk kwatancen sun kasance masu mahimmanci a kididdigar, duk nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan sun faru. Semaglutid yana da alaƙa da ƙananan abubuwan da ba su da kyau ga kowane nau'in BMI (<30, 30 zuwa <35, 35 zuwa <40, da ≥40 kg/m²), semaglutide yana da ƙananan ƙananan abubuwan da suka faru (abubuwan da suka faru a cikin shekaru 100 na mutum: 43.23, 451.70, da 651.54). 50.48, 49.66, 52.73, da 60.85 don placebo).
Illar Rage Nauyi a cikin Mutane masu Kiba ko Kiba ba tare da Metabolism ba:
Bita na tsari ya kimanta inganci da amincin semaglutide a cikin mutane masu kiba ko masu kiba ba tare da metabolism ba [11] . Wannan bita ya haɗa sakamako daga gwaje-gwajen asibiti da yawa, yana nuna tasirin semaglutide akan asarar nauyi, sigogi na rayuwa, da sakamakon kiwon lafiya gabaɗaya. Binciken da aka nuna yana da alaƙa da semaglutide tare da babban asarar nauyi da haɓakawa a cikin ma'aunin kiwon lafiya da ke da alaƙa da kiba, yana ba da shawarar yuwuwar sa azaman zaɓi mai mahimmanci na jiyya ga marasa lafiya masu kiba.
Illar Rage Nauyi a cikin Marasa lafiya marasa ciwon sukari (Shaida daga RCT da yawa):
Gwaje-gwajen da bazuwar bazuwar guda huɗu (RCTs) waɗanda suka haɗa da marasa lafiya tare da ma'aunin asali na 96-105 kg sun kimanta mako-mako na 2.4 MG subcutaneous semaglutide tare da tsarin rayuwa (nasiha, abinci, aikin jiki) don asarar nauyi [12] . Ɗaya daga cikin RCT a cikin marasa lafiya marasa ciwon sukari (N = 1,961) ya ruwaito ma'anar asarar 15% (15 kg) vs. 2% (3 kg) tare da placebo bayan makonni 68 (ƙididdiga mai mahimmanci). Yawan marasa lafiya da suka samu ≥5% asarar nauyi shine 86% vs. 32% (lambar da ake buƙata don magance [NNT] = 2), kuma ≥10% asarar nauyi shine 69% vs. 12% (NNT = 2). Rage nauyi a cikin makonni ~ 60. Abubuwan da ba su da kyau na Gastrointestinal (AEs) sun faru a cikin 74% vs. 48% (lambar da ake buƙata don cutar da [NNH] = 3). Kashewa saboda AEs shine 7% vs. 3% (NNH = 25). An lura da irin wannan sakamakon a cikin wani RCT tare da tsaka-tsakin salon rayuwa (N = 611): semaglutide ya haifar da 16% (17 kg) vs. 6% (6 kg) asarar nauyi. A cikin binciken bincike-bincike na RCT a cikin marasa lafiya marasa ciwon sukari (N = 1,210), mako-mako 2.4 mg semaglutide, 1.0 mg semaglutide, ko placebo ya haifar da asarar nauyi na 10%, 7%, da 3% bayan makonni 68. Matsakaicin samun ≥5% asarar nauyi shine 69% (2.4 mg), 57% (1.0 mg), da 29% (placebo). Don 2.4 MG vs. 1.0 MG, NNT = 9. Bayanan martaba na AE sun kasance daidai a cikin allurai. A cikin nauyin kula da RCT (N = 803), mahalarta marasa ciwon sukari sun karbi 2.4 MG semaglutide mako-mako don makonni 20, sannan an bazu su don ci gaba da semaglutide ko canzawa zuwa placebo. Bayan makonni 48, masu amfani da semaglutide sun ci gaba da rasa 8% vs. placebo masu amfani da samun 7%.
A taƙaice, semaglutide shine GLP-1 agonist mai karɓa tare da ƙimar aikace-aikacen yanki da yawa. A cikin jiyya na metabolism, yana ɗaure ga masu karɓar GLP-1 don haɓaka haɓakar insulin da hana sakin glucagon, yadda ya kamata sarrafa matakan glucose na jini da kuma samar da zaɓi mai mahimmanci ga marasa lafiya tare da nau'in metabolism na 2. A fagen kula da kiba, semaglutide na iya rage yawan kuzarin kuzari ta hanyar dabaru irin su hana ci abinci na tsakiya da jinkirta zubar da ciki, yana taimakawa marasa lafiya masu kiba su rasa nauyi da inganta yanayin rayuwa. Bugu da ƙari, semaglutide yana nuna yuwuwar aikace-aikacen aikace-aikace a cikin rigakafi da kuma kula da cututtukan zuciya, da haɓakar abubuwan haɗarin cututtukan zuciya yana ba da sabuwar hanyar rage abubuwan da ke faruwa na cututtukan zuciya. Bayyanar semaglutide ba wai yana wadatar hanyoyin magance cututtukan da ke da alaƙa ba amma kuma yana kawo sabon bege don inganta ingancin rayuwa da lafiyar marasa lafiya.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Hegner P mai bincike ne a Jami'ar Regensburg. Ayyukansa sun haɗa da Chemistry, Tsarin zuciya, da Ilimin zuciya. A cikin Chemistry, yana bincika halayen da ke da alaƙa da lafiyar zuciya. A cikin nazarin tsarin zuciya na zuciya, yana bincikar zuciya da ayyuka na jirgin ruwa, yana neman fahimtar hanyoyin warkewa. Binciken ilimin zuciyarsa yana mai da hankali kan rigakafin cututtukan zuciya, ganowa, da magani.
Gudunmawar Hegner tana da mahimmanci. Bayanan sinadarai nasa sun haifar da sabon ci gaban magungunan cututtukan zuciya. Ayyukansa akan hanyoyin zuciya da na jirgin ruwa sun inganta fahimtar cututtukan zuciya. A asibiti, bincikensa ya inganta tsarin kula da cututtukan zuciya, yana haɓaka matakan kulawa da marasa lafiya. Gabaɗaya, tsarin koyarwa da yawa na Hegner yana wadatar da maganin cututtukan zuciya, yana ba da bege don rage nauyin cututtuka da ingantacciyar sakamako mai haƙuri. An jera Hegner P a cikin ambaton ambaton [8].
