By Cocer Peptides 
Watanni 2 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da kowane yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Yayin da ake ci gaba da samun karuwar cututtukan cututtukan da suka hada da kiba, kiba, da metabolism a duniya, neman ingantattun magungunan warkewa ya zama babban batu a fannin likitanci. Maz, a matsayin novel dual agonist agonist, na iya kunna mai karɓar GLP-1 lokaci guda da mai karɓar glucagon, kuma ana tsammanin zai taka muhimmiyar rawa wajen asarar nauyi da sarrafa sukarin jini, yana ba da sabbin dama don maganin cututtukan rayuwa.
Hoto 1 Tsarin sinadaran Maz.
Bayanin Maz
Maz shine GLP-1/glucagon dual receptor agonist, sabon magani ne don maganin cututtukan rayuwa. A cikin 'yan shekarun da suka gabata, ci gaban miyagun ƙwayoyi da ke niyya da cututtukan da ke rayuwa ya ci gaba da ci gaba. GLP-1 agonists masu karɓa da glucagon agonists sun nuna wasu tasirin warkewa lokacin amfani da su kaɗai, amma kuma suna da nasu iyakokin. Don neman mafi kyawun zaɓi na magani, masu bincike sun mayar da hankali kan haɓaka magunguna waɗanda za su iya yin aiki akan maƙasudi da yawa lokaci guda, haifar da ƙirƙirar Maz. Tsarin ci gabanta ya sami ingantaccen nazari mai zurfi da gwaje-gwaje na asibiti da yawa, a hankali yana tabbatar da amincinsa da ingancinsa.
Tsarin Aiki
(1) Kunna mai karɓar GLP-1
Tsarin glucose homeostasis na jini: GLP-1 shine hormone peptide wanda aka ɓoye ta ƙwayoyin L na hanji. Bayan kunna mai karɓar GLP-1, Maz yana daidaita glucose na jini ta hanyoyi da yawa. Yana haɓaka siginar insulin ta ƙwayoyin β pancreatic, yana haɓaka haɓakar insulin, ta haka yana haɓaka ɗaukar glucose da amfani, da rage matakan glucose na jini. Yana hana fitowar glucagon daga sel na pancreatic α kuma yana rage fitowar glucose na hanta, yana ƙara tabbatar da daidaiton glucose na jini.
Jinkirta Bakin ciki: Maz yana kunna mai karɓar GLP-1, yana aiki akan tsarin juyayi na gastrointestinal don rage zubar ciki. Wannan yana tsawaita riƙon abinci a cikin ciki, ƙara yawan gamsuwa da rage cin abinci, don haka yana taimakawa sarrafa nauyi.
Tsarin ci: Bayan kunna mai karɓar GLP-1, ana watsa sigina zuwa tsarin kulawa na tsakiya, yana aiki akan cibiyar ciyar da hypothalamic don daidaita ɓoyewar neuropeptides da ke da alaƙa da ci, kamar rage maganganun neuropeptide Y (NPY) da haɓaka proopiomelanocortin (POMC) magana, ta haka ne ya haifar da cikar abinci.
(2) Kunna masu karɓar glucagon
Haɓaka kashe kuzarin kuzari: Lokacin da mai karɓar glucagon ya kunna ta Maz, yana haɓaka faɗuwar kitse da fatty acid oxidation, ƙara yawan kashe kuzari. Bugu da ƙari, yana haɓaka bayanin furotin 1 (UCP1) wanda ba a haɗa shi ba, yana haɓaka thermogenesis a cikin nau'in adipose mai launin ruwan kasa, yana ƙara haɓaka ƙarfin kuzarin jiki da taimakawa cikin asarar nauyi.
Tsarin metabolism na glucose: Kunna masu karɓar glucagon yana haɓaka hanta glycogenolysis da gluconeogenesis. Koyaya, a ƙarƙashin tasirin Maz, wannan tasirin talla ba wai kawai yana haɓaka matakan glucose na jini ba amma a maimakon haka yana samun daidaitaccen tsarin glucose na jini ta hanyar hulɗar haɗin gwiwa tare da tasirin kunna mai karɓa na GLP-1. Lokacin da matakan glucose na jini ya yi girma, tasirin hypoglycemic wanda ke daidaitawa ta hanyar kunna mai karɓa na GLP-1 ya mamaye; lokacin da matakan glucose na jini ya yi ƙasa, tasirin hyperglycemic wanda ke daidaitawa ta hanyar kunna mai karɓar glucagon yana hana hypoglycemia.
(3) Injiniya Haɗin kai
Maz a lokaci guda yana kunna duka masu karɓar GLP-1 da masu karɓar glucagon. Hanyoyin siginar da waɗannan masu karɓa guda biyu ke kunnawa suna aiki tare da juna don aiwatar da ingantaccen sakamako mai ƙarfi na tsarin rayuwa. Dangane da asarar nauyi, kunna mai karɓa na GLP-1 yana rage yawan kuzari ta hanyar hana ci abinci da jinkirta zubar da ciki, yayin da kunna mai karɓar glucagon yana haɓaka kashe kuzari. Ayyukan haɗin gwiwa na duka masu karɓa sun fi dacewa da samun raguwar nauyi. Dangane da ka'idojin glucose na jini, tasirin abubuwan kunnawa masu karɓa guda biyu suna haɗawa da juna don kiyaye glucose na jini tsakanin kewayon al'ada da kuma guje wa juzu'i mai yawa.
3. Tasirin Jiki
(1) Illar Rage Nauyi
Shaidar asibiti: Gwajin gwaji da yawa sun nuna cewa Maz yana da tasirin asarar nauyi. A cikin binciken da aka yi niyya ga manya ko manya a cikin , 24 makonni na Maz magani (tare da matsakaicin adadin 6 MG) ya haifar da asarar nauyi na 6.7% -11.3%, yayin da ƙungiyar placebo ta sami karuwar 1.0% nauyi. Daga cikin ƙungiyoyi daban-daban, Maz a 4.5 MG da 6 MG sun nuna ƙarin tasirin asarar nauyi, tare da bambance-bambancen magani idan aka kwatanta da placebo daga -7.7% zuwa -12.3% (P <0.0001). A cikin bita na yau da kullun da meta-bincike da ke tattare da mahalarta 680, Maz ya nuna babban fa'ida akan placebo a cikin raguwar nauyi, tare da ma'anar ma'anar (MD) na -6.22% (95% tazarar amincewa [CI]: -8.02% zuwa -4.41%).
Hoto 2 Ƙarshen ingancin ingancin nauyin jiki. Canjin kashi kashi daga asali a cikin nauyin jiki a mako na 24. b Canjin kashi daga tushe a cikin nauyin jiki akan lokaci.
(2) Tasirin Ka'idojin Glycemic
Tasiri a kan marasa lafiya tare da nau'in metabolism na nau'in 2: Ga marasa lafiya tare da nau'in 2 na metabolism, Maz yana rage yawan haemoglobin A1c (HbA1c) da matakan glucose na jini yadda ya kamata. A cikin bazuwar da aka danganta, makafi biyu, gwajin gwaji na gwaji na gwaji na gwaji na gwaji na 2, marasa lafiya da nau'in 2 na metabolism waɗanda suka karɓi maganin Maz (a matsakaicin adadin 6 MG) na makonni 20, sun nuna matsakaicin canji a cikin HbA1c daga -1.41% zuwa -1.67%, yayin da ƙungiyar placebo ta nuna canji na 0.03% mai mahimmanci, idan aka kwatanta da 0.03%. 0.0001). Har ila yau, marasa lafiya sun sami raguwa mai yawa a cikin nauyin jiki, tare da matsakaicin matsakaicin canji yana nuna dangantakar da ke dogara da kashi, wanda ya kai har zuwa -7.1%.
Fa'idodi a cikin tsarin glucose na jini: Maz ba kawai yana rage matakan glucose na jini ba har ma yana inganta canjin glucose na jini kuma yana rage haɗarin abubuwan hypoglycemic. Idan aka kwatanta da magungunan antidiabetic na gargajiya, tsarin aikin agonist mai karɓar mai karɓa na biyu yana samun ƙarin daidaitaccen tsarin glucose na jini, ta haka yana haɓaka ingancin rayuwa na marasa lafiya da tsinkaye na dogon lokaci.
(3) Tasiri akan alamomin zuciya da jijiyoyin jini
Tsarin hawan jini: Maz yana rage karfin jini na systolic da diastolic. Binciken na yau da kullum da nazarin meta-bincike ya nuna cewa idan aka kwatanta da placebo, Maz yana rage karfin jini na systolic ta matsakaicin bambanci (MD) na -7.57 mmHg (95% CI: -11.17 zuwa -3.98 mmHg); don rage hawan jini na diastolic, MD ya kasance -2.98 mmHg (95% CI: -5.74 zuwa -0.22 mmHg). Ana iya danganta wannan ga hanyoyin Maz da yawa, gami da haɓaka aikin jijiyoyi na jijiyoyi, rage juriya na jijiyoyi, da daidaita ma'aunin ruwa-sodium.
Tsarin lipid: Maz yana daidaita bayanan bayanan lipid yadda ya kamata. Yana rage jimlar cholesterol (MD = -16.82%, 95% CI: -24.52 zuwa -9.13%), triglycerides (MD = -43.29%, 95% CI: -61.57 to -25.01%), da low-density lipoprotein (MD = -17.05% . -2%) zuwa 4:4. matakan, yayin da kuma yin wani tasiri na tsari akan babban adadin lipoprotein (MD = -7.54%, 95% CI: -11.26 to -3.83%). Wadannan tasirin suna taimakawa rage haɗarin cututtukan zuciya da jijiyoyin jini kuma suna da tasirin kariya akan tsarin zuciya.
(4) Tasiri kan hyperuricemia
Shaidar gwaji ta dabba: A cikin nazarin ƙirar bera na hyperuricemia (HUA), allurar subcutaneous na 0.05 mg/kg da 0.075 mg/kg na Maz (kowace kwanaki 3) ya rage yawan matakan serum uric acid (SUA) a cikin berayen. Idan aka kwatanta da ƙungiyar HUA, SUA da matakan serum creatinine (SCr) sun ragu sosai a cikin ƙungiyoyin Maz-MD da Maz-HD, kuma matakan furotin na fitsari (U-Pro) sun ragu sosai a cikin ƙungiyar Maz-MD. Bugu da ƙari, Maz ya inganta sauye-sauyen tarihin cututtukan koda a cikin berayen HUA.
Hoto 3 a: Canjin kashi dari daga asali a cikin nauyin jiki akan lokaci. b: Adadin mahalarta da suka kai ga asarar nauyi.
Binciken Aikace-aikacen
(1) Ci gaban gwaji na asibiti
Gwaji na Farko na Farko: Farkon gwajin asibiti na Farko na farko sun tantance aminci, juriya, da ingancin farko na Maz. A cikin bazuwar, mai sarrafa wuribo, gwaji-yawan haɓakawa mataki na 1b, manya waɗanda suka yi kiba ko kiba an ba su allurai daban-daban na Maz (har zuwa 10 MG). Sakamakon ya nuna cewa Maz yana da kyau a cikin wannan nau'i na nau'i, ba tare da wani mummunan mummunan abu da aka ruwaito ba, kuma an lura da asarar nauyi.
Gwajin asibiti na Mataki na 2: Gwajin asibiti na mataki na 2 ya ƙara tabbatar da inganci da amincin Maz a cikin mutane daban-daban. A cikin gwaji na Mataki na 2 da aka yi niyya ga marasa lafiyar Sinawa tare da nau'in metabolism na nau'in 2, Maz ya nuna tasiri mai mahimmanci wajen rage HbA1c da nauyin jiki, tare da aminci mai kama da rukunin placebo. Halayen halayen gama gari sun kasance masu sauƙi zuwa matsakaicin halayen ciki, kamar gudawa da tashin zuciya. A cikin gwaji na Mataki na 2 wanda ke niyya da kiba ko manya masu kiba, makonni 24 na jiyya na Maz (har zuwa 6 MG) ya nuna ingantaccen ingantaccen nauyi da aminci.
(2) Nazarin Kwatancen da Sauran Magunguna
Kwatanta tare da GLP-1 agonists mai karɓa: Idan aka kwatanta da na gargajiya GLP-1 agonists, Maz na iya samun ƙarin tasiri mai mahimmanci akan asarar nauyi da tsarin glucose na jini saboda kunnawa biyu na masu karɓar GLP-1 da masu karɓa na glucagon. A wasu nazarin, Maz ya sami asarar nauyi fiye da wasu agonists masu karɓa na GLP-1 a cikin lokacin jiyya ɗaya kuma ya nuna ingantaccen kwanciyar hankali a cikin sarrafa glucose na jini.
Kwatanta da sauran magungunan ciwon sukari: Idan aka kwatanta da magungunan maganin ciwon sukari na gargajiya, Maz ba wai kawai rage glucose na jini yadda ya kamata ba amma yana ba da ƙarin fa'idodi kamar asarar nauyi da ingantattun alamomin rayuwa na zuciya da jijiyoyin jini.
Kammalawa
A matsayin GLP-1/glucagon dual agonist mai karɓa, Maz yana samun cikakkiyar tsari na metabolism na makamashi, glucose na jini, hawan jini, da lipids na jini ta hanyar kunna mahimman masu karɓar tsarin rayuwa guda biyu, yana nuna ƙarin fa'ida da tasirin warkewa fiye da agonists mai karɓa guda ɗaya. Maz yana da alƙawari mai mahimmanci don cututtuka daban-daban na rayuwa, gami da kiba, nau'in metabolism na 2, da hyperuricemia.
Sources
[1] Zhang B, Cheng Z, Chen J, et al. Inganci da Tsaron Maz a cikin Majinyatan Sinawa tare da Nau'in Metabolism Nau'in 2: Bazuwar, Makafi Biyu, Gwajin Mataki na 2 Mai Sarrafa Wuri[J]. Kulawar Metabolism, 2024,47 (1): 160-168.DOI: 10.2337 / dc23-1287.
[2] Nalisa DL, Cuboia N, Dyab E, et al. Inganci da amincin Maz akan asarar nauyi tsakanin masu ciwon sukari da marasa ciwon sukari: nazari na yau da kullun da meta-bincike na gwaje-gwajen da bazuwar [J]. Iyakoki a cikin Ilimin Ilimin Halittu, 2024,15. https://api.semanticscholar.org/CorpusID:267984513.
[3] Ji L, Jiang H, Cheng Z, et al. Gwajin gwaji na mazdutide na zamani na 2 a cikin manya masu kiba na kasar Sin ko manya masu kiba[J]. Sadarwar yanayi, 2023,14 (1): 8289.DOI: 10.1038 / s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: Littafin Glucagon-Kamar Peptide-1 (GLP-1R) da Glucagon (GCGR) Mai karɓar Dual Agonist, Maz (IBI362), Yana haɓaka Hyperuricemia a cikin berayen Hyperuricemic [J]. Metabolism, 2023. https://api.semanticscholar.org/CorpusID:259452040
[5] Ji L, Gao L, Jiang H, et al. Aminci da inganci na GLP-1 da glucagon receptor dual agonist mazdutide (IBI362) 9 MG da 10 MG a cikin manya na kasar Sin masu kiba ko kiba: Bazuwar, sarrafa wuribo, yawan hawan-hawan kashi 1b gwaji [J]. Eclinicalmedicine, 2022,54:101691.DOI:10.1016/j.elinm.2022.101691.
Samfura akwai don amfani da bincike kawai:
