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1 kits (10 Vials)
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▎ Tsarin Tirzepatide
Source: PubChem |
Jeri: Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Leu-Asp-Lys-Ile-Ala-Gln-{diacid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Tsarin kwayoyin halitta: C 225H 348N 48O68 Nauyin Kwayoyin: 4813 g/mol Lambar CAS: 2023788-19-2 Kamfanin CID na PubChem: 163285897 Synonyms: Zepbound; Munjaro |
▎ Binciken Tirzepatide
Menene asalin binciken Tirzepatide?
Tirzepatide shine maganin polypeptide na roba. Ci gabanta ya samo asali ne daga zurfin fahimtar iyakokin GLP-1 masu karɓar agonists masu karɓa a cikin jiyya na nau'in 2 na metabolism (T2DM) da kiba. Kodayake GLP-1 agonists masu karɓa sun nuna kyakkyawan aiki a cikin sarrafa glucose na jini da kuma asarar nauyi, masana kimiyya sun gano cewa kunna su na mai karɓar GIP yana da rauni sosai, wanda ke iyakance tasirin warkewa na kwayoyi. Sabili da haka, ƙungiyar bincike da haɓakawa sun himmatu don haɓaka sabon nau'in magani wanda zai iya kunna duka GIPR da GLP-1R lokaci guda, da nufin cimma cikakkiyar ingantaccen kulawar glucose na jini da sarrafa nauyi [1].
A yayin aiwatar da bincike da ci gaba, masana kimiyya sun gudanar da babban adadin bincike na bincike da gwaji na asibiti. A cikin matakin bincike na farko, an kimanta kaddarorin magunguna na Tirzepatide sosai ta hanyar gwaje-gwajen dabba, yana tabbatar da yuwuwar sa a cikin sarrafa glucose na jini da asarar nauyi. Sakamakon ya nuna cewa zai iya rage yawan matakan glucose na jini a cikin nau'ikan dabbobi kuma ya nuna kyakkyawan aiki a cikin sarrafa nauyi, yana kafa harsashin gwaji na asibiti na gaba.
Bayan haka, matakin gwajin asibiti ya haɗa da gwaji na Phase I, II, da III. Gwajin Mataki na I ya fi kimanta aminci, juriya, da kaddarorin magunguna na maganin. Sakamakon ya nuna cewa Tirzepatide yana da kyakkyawan aminci da haƙuri. Gwajin Mataki na II ya kara bincika inganci da amincin allurai daban-daban na Tirzepatide a cikin marasa lafiya tare da T2DM, da farko yana ƙayyade iyakar adadin sa. Mafi mahimmancin gwaji na asibiti na Mataki na III, kamar su jerin binciken SURPASS, sun haɗa da adadi mai yawa na marasa lafiya tare da T2DM. Sakamakon ya nuna cewa Tirzepatide ya fi girma fiye da masu karɓar masu karɓa na GLP-1 na yanzu, irin su semaglutide, a rage yawan glucose na jini da nauyi, yana ba da shaida mai karfi don aikace-aikacen tallan Tirzepatide [1].
Menene tsarin aikin Tirzepatide?
Tirzepatide yana rage glucose na jini ta hanyoyi da yawa da ke aiki tare. Lokacin kunna mai karɓar GLP-1, Tirzepatide yana ɗaure ga mai karɓar GLP-1 akan ƙwayoyin β-pancreatic, yana kwaikwayon aikin GLP-1 na halitta. GLP-1 hormone ne da aka samar a cikin hanji kuma yana da mahimmanci don kiyaye glucose homeostasis. Yana iya haɓaka haɓakar insulin, ɓoyewa, da fahimtar glucose, rage ƙwayar glucagon don haɓaka satiety, kuma yana hana ci.
Wannan kunnawa na iya haɓaka ƙwayar insulin. Insulin shine babban hormone hypoglycemic a cikin jiki, wanda zai iya ƙara haɓakawa da kuma amfani da glucose ta sel, ta haka ne rage matakan glucose na jini. A cikin marasa lafiya tare da T2DM, ɓoyewar insulin bai isa ba ko kuma hankalin sel ga insulin ya ragu, yana haifar da haɓakar glucose na jini. Ta hanyar kunna mai karɓar GLP-1, Tirzepatide yana ƙara haɓakar insulin, wanda ke taimakawa haɓaka sarrafa glucose na jini.
A lokaci guda, kunna mai karɓar GLP-1 shima yana hana sakin glucagon. Glucagon yawanci yana haɓaka glycogenolysis da gluconeogenesis yayin azumi, yana haɓaka samar da glucose na jini. Ta hanyar hana aikin glucagon, Tirzepatide yana ƙara rage tushen glucose na jini, yana ba da gudummawa ga sarrafa glucose na jini [2]..
Lokacin kunna mai karɓar GIP, Tirzepatide yana aiki akan mai karɓar GIP a lokaci guda. Bayan kunnawa, yana iya haɓaka ji na insulin da ɓoyewa. Mai karɓar GIP yana samuwa a cikin kyallen takarda kamar ƙwayoyin β-pancreatic. Bayan kunnawa, ta hanyar watsa hanyoyin siginar siginar ciki, ƙwayar insulin yana ƙaruwa, kuma ana samun ingantaccen amsawar kwayar halitta ga insulin, don haka mafi inganci rage glucose na jini.
Tirzepatide shine nau'in farko-in-aji dual glucagon-kamar peptide-1 da glucose-dependent insulinotropic polypeptide (GIP) analog, wanda aka amince da shi don kula da tsofaffi marasa lafiya tare da T2DM a matsayin haɗin gwiwa ga abinci da motsa jiki. Tirzepatide shine tsarin sinadarai na roba wanda ya dogara da jerin GIP, wanda ya ƙunshi peptide 39-amino acid. Yana kara samar da insulin, yana rage sakin glucagon ta hanyar dogaro da glucose, yana rage azumi da matakan glucose na jini, yana inganta wadatuwa, yana rage nauyin jiki, yana jinkirta fitar da ciki. Wannan tasirin agonist mai karɓa na dual yana sa Tirzepatide ya fi tasiri fiye da GLP-1 agonists mai karɓa guda ɗaya a cikin haɓaka ƙwayar insulin da hana sakin glucagon [2].
Tirzepatide kuma na iya jinkirta zubar da ciki da kuma kara satiety. Yana iya jinkirta zubar da ciki, yana tsawaita lokacin zama na abinci a cikin ciki da rage yawan sha na abubuwan gina jiki, don haka guje wa hauhawar glucose na jini bayan cin abinci. A cikin binciken da ba na asibiti da na asibiti ba, tasirin Tirzepatide akan zubar da ciki yana kama da na GLP-1 agonists mai karɓa. A cikin ƙananan berayen da ke haifar da abinci, ƙimar jinkirin zubar da ciki ta hanyar Tirzepatide yayi kama da na semaglutide, amma waɗannan mummunan tasirin hanawa suna ɓacewa bayan makonni 2 na jiyya.
A cikin mahalarta tare da kuma ba tare da T2DM ba, Tirzepatide sau ɗaya-mako (≥5 MG da ≥4.5 MG, bi da bi) yana jinkirta zubar da ciki bayan kashi ɗaya. A cikin mahalarta masu lafiya, an rage tasirin sakamako bayan yawancin allurai na Tirzepatide ko dulaglutide (Urva S, 2020). A lokaci guda kuma, yana iya yin aiki akan tsarin juyayi na tsakiya, ƙara yawan satiety, rage ci, da cin abinci. Ta hanyar sarrafa abin da ake ci, a kaikaice yana taimakawa wajen sarrafa matakan glucose na jini, musamman dacewa da matsalar kiba sau da yawa tare da marasa lafiya tare da T2DM, kuma yana taimakawa haɓaka juriya na insulin da yanayin rayuwa gaba ɗaya [2].
An gano Tirzepatide don haɓaka matakin adiponectin, adipocytokine mai alaƙa da hankalin insulin. Ƙara yawan matakan adiponectin yana taimakawa wajen inganta haɓakar insulin, yana sa sel su zama masu amsawa ga insulin, don haka ya fi dacewa da karɓa da amfani da glucose da kuma rage glucose na jini [2] . Bugu da ƙari, Tirzepatide kuma zai iya inganta bayanin martabar lipid kuma yana da tasirin kariya ga lafiyar zuciya. An tabbatar da cewa Tirzepatide zai iya inganta hawan jini, rage ƙananan ƙwayar lipoprotein (LDL) cholesterol da triglycerides [3] , yana kara tallafawa cikakken amfaninsa a cikin sarrafa glucose na jini.
Source: PubMed [5]
Bincike mai alaƙa
Inganci akan sarrafa nauyi a cikin marasa lafiya tare da kiba da nau'in 2 metabolism
Yawancin karatu na asibiti sun tabbatar da mahimmancin tasirin Tirzepatide a cikin sarrafa nauyin jiki a cikin marasa lafiya da kiba da T2DM. A cikin wani bincike mai suna 'SURMOUNT-2', wanda shine mataki na 3, makafi biyu, bazuwar, gwajin sarrafa wuribo da aka gudanar a cikin ƙasashe bakwai. Manya (shekaru ≥18 shekaru) tare da ma'auni na jiki (BMI) na 27 kg / m² ko sama da matakin glycated haemoglobin (HbA₁c) na 7 - 10% an ba da izini don karɓar allurar Tirzepatide na subcutaneous sau ɗaya a mako-mako (10 mg ko 15 mg) ko placebo na makonni 72.
Sakamakon ya nuna cewa a cikin mako 72, yawan asarar nauyi a cikin Tirzepatide 10 MG da 15 MG shine -12.8% da -14.7%, bi da bi, idan aka kwatanta da -3.2% a cikin rukunin placebo. Matsakaicin bambance-bambancen jiyya na Tirzepatide 10 MG da 15 MG idan aka kwatanta da placebo sune -9.6 kashi kashi da -11.6 kashi kashi, bi da bi, dukansu sun kasance masu mahimmanci (p <0.0001). Bugu da ƙari, yawancin marasa lafiya da ke karɓar maganin Tirzepatide sun kai iyakar asarar nauyi na 5% ko fiye (79 - 83% vs 32%) [4].
A cikin binciken 'SURMOUNT-2', matsakaicin matsakaicin nauyi shine 100.7 kg, BMI shine 36.1 kg/m², kuma HbA₁c ya kasance 8.02%. Bayan makonni 72 na jiyya, Tirzepatide ba kawai rage nauyin jiki sosai ba amma kuma yana da tasiri mai kyau akan sarrafa glucose na jini [4].
Tasirin haɓakawa akan neuropathy masu alaƙa da metabolism
Nazarin ome sun nuna cewa GLP1-RAs na iya rage haɗarin lalata a cikin marasa lafiya tare da T2DM ta hanyar inganta ƙwaƙwalwar ajiya, koyo, da kuma shawo kan rashin fahimta. A matsayin GIP-RA / GLP-1RA dual, Tirzepatide an yi nazari a cikin layin kwayoyin neuroblastoma (SHSY5Y) don tasirinsa akan alamun ci gaban neuronal (CREB da BDNF), apoptosis (RAX / Bcl2 rabo), bambanci (pAkt, MAP2, GAP43, da AGBL4), da insulin juriya (GBSLUT1), da kuma insulin juriya (GBSLUT1).
Sakamakon a karon farko ya jaddada rawar da Tirzepatide ke takawa wajen kunna hanyar pAkt/CREB/BDNF da siginar sigina na ƙasa, da kuma tasirin sa na neuroprotective. Hakanan ya nuna cewa Tirzepatide ya sami damar magance tasirin da ke da alaƙa da hyperglycemia da juriya na insulin a matakin neuronal. Sabili da haka, Tirzepatide na iya inganta haɓakar neurodegeneration da ke haifar da hyperglycemia kuma ya shawo kan juriya na insulin na neuronal, yana ba da sabbin fahimta don haɓakar cututtukan cututtukan da ke da alaƙa da metabolism [5]..
Ci gaban bincike a cikin jiyya na nau'in 2 metabolism
Wasu nazarin sun nuna cewa a matsayin sabon nau'in maganin hypoglycemic, Tirzepatide ya zama agonist na GIP / GLP-1R na farko da aka amince da shi don maganin metabolism a cikin Amurka. An tabbatar da cewa yana da tasiri mai mahimmanci akan rage yawan glucose na jini da rage nauyin jiki a cikin gwaje-gwaje masu yawa na asibiti, kuma akwai shaidun da ke nuna cewa yana da babban tasiri a cikin kariya ta zuciya.
Bugu da ƙari, ra'ayin peptides na roba ya buɗe yawancin yiwuwar da ba a sani ba don Tirzepatide. Gwaje-gwajen da ke gudana (NCT04166773) da shaidu sun nuna cewa ya zama magani mai ban sha'awa a cikin fagage irin su cututtukan hanta maras barasa (NAFLD), kariya ta koda, da kariya ta neuroprotection [6].
Sakamakon dogon lokaci na tirzepatide akan lafiyar zuciya da jijiyoyin jini
Tirzepatide na iya rage haɗarin cututtukan cututtukan zuciya ta hanyar haɓaka asarar nauyi. Wani binciken yayi nazarin tasirin Tirzepatide akan kiba da cututtukan cututtukan zuciya a cikin manya na Amurka (Wong ND, 2024). Binciken ya gano cewa a cikin manya na Amurka da suka cancanci maganin Tirzepatide, bayan jiyya tare da 15 MG na Tirzepatide, an kiyasta cewa 70.6% da 56.7% na manya suna da asarar nauyi na ≥15% da ≥20%, bi da bi, wanda ke nufin raguwar 58.8% na yawan mutanen da ke da kiba.
Daga cikin wadanda ba tare da cututtukan zuciya ba, kimanin shekaru 10 da aka kiyasta hadarin cututtukan zuciya na zuciya ya ragu daga 10.1% 'kafin magani' zuwa 7.7% 'bayan magani', yana nuna cikakkiyar raguwar haɗarin 2.4% da raguwar haɗarin dangi na 23.6%, wanda ke nufin cewa za a iya hana 2 miliyan cututtukan cututtukan zuciya a cikin shekaru 10.
A ƙarshe, Tirzepatide wani labari ne mai dual agonist na GIP da masu karɓar GLP-1, wanda ke da mahimmanci a cikin kula da T2DM da kiba. Zai iya inganta haɓakar ƙwayar insulin yadda ya kamata, hana ƙwayar glucagon, daidaita daidaitaccen glucose na jini, rage haɗarin rikitarwa, haɓaka aikin β-cell na pancreatic, da jinkirta ci gaban metabolism. Har ila yau, yana da tasirin kariya akan tsarin zuciya da jijiyoyin jini.
A wajen maganin kiba, yana iya rage cin abinci yadda ya kamata, rage sha’awa, kara koshi, taimaka wa masu kiba su rage kiba, da rage hadarin da ke da alaka da kiba. Hakanan yana iya haɓaka juriya na insulin da metabolism na lipid. Bugu da ƙari, ya nuna yuwuwar a cikin maganin cututtukan da ke da alaƙa da rikice-rikice irin su steatohepatitis mara-giya, ciwo na bacci, da gazawar zuciya. Yana iya inganta mahara na rayuwa Manuniya lokaci guda, samar da mafi m magani shirin.
Tsarin allurar sa na sati-sati ya dace don amfani kuma yana iya inganta yarda da jiyya na 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
Dokta William T. Garvey fitaccen malami ne kuma mai bincike da ke da alaƙa da manyan cibiyoyi masu daraja, ciki har da Jami'ar Alabama a Birmingham, Jami'ar Aston, da Cibiyar Kiwon Lafiyar Tsohon Soja ta Birmingham. Asalin iliminsa da ƙwarewar ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun likitocin da kimiyya. Dokta Garvey ya ba da gudummawa mai mahimmanci ga fannonin ilimin endocrinology da metabolism, abinci mai gina jiki da abinci mai gina jiki, biochemistry da ilmin kwayoyin halitta, da kuma magani na gabaɗaya da na ciki, tare da mai da hankali kan tsarin zuciya da jijiyoyin jini. An san aikinsa sosai kuma an girmama shi sosai, musamman ana kiransa da Babban Mai Binciken Bincike a cikin Yankin Cross-Field na 2023 da 2024, yana nuna babban tasiri da tasirin bincikensa akan al'ummar kimiyya.
Dokta Garvey's bincike sha'awa da gwaninta ya fadada zuwa sassa daban-daban na cututtuka na rayuwa da sarrafa su. Ya kasance mai himma sosai a cikin nazarin metabolism metabolism, kiba, da rikice-rikicen da ke tattare da su, da nufin buɗe sabbin dabarun warkewa da haɓaka sakamakon haƙuri. Ayyukansa sun ƙunshi bincike na kimiyya na asali, gwaje-gwaje na asibiti, da nazarin fassarar fassarar, ƙaddamar da rata tsakanin binciken dakin gwaje-gwaje da aikace-aikacen likita na ainihi. Ta hanyar bincike mai zurfi, Dokta Garvey ya ba da gudummawa ga zurfin fahimtar hanyoyin da ke tattare da rikice-rikice na rayuwa kuma ya taimaka wajen tsara ka'idodin asibiti da ka'idojin magani a fagen ilimin endocrinology da metabolism. Dr. William T. Garvey an jera shi a cikin ambaton ambaton [4].
