Cocer Peptides fɛ 
a bɛ kalo 2 bɔ
BƐƐRƐ KUNNAFONIW NI FƐRƐW KUNNAFONIW BƐƐ MIN BƐ NI WEBSITE KAN NA, olu BƐ KUNNAFONIW FƆLƆ DƆRƆN NI KALANSENW YE.
Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *glasi kɔnɔ*, o kɔrɔ ye gilasi kɔnɔ) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki ka dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.
Ikomi farikoloɲɛnajɛ banaw i n’a fɔ farikolo girinya, fasa, ani farikoloɲɛnajɛ bɛ ka caya diɲɛ kɔnɔ, furakɛli fura minnu bɛ se ka kɛ kosɛbɛ, olu ɲinini kɛra barokun ye min bɛ fɔ kosɛbɛ furakɛli siratigɛ la. Maz, n’o ye agoniste fila-fila kura ye, o bɛ se ka GLP-1 minɛbaga ni glucagon minɛbaga baara waati kelen na, wa a jirala ko a jɔyɔrɔ kɛrɛnkɛrɛnnen don farikolo girinya dɔgɔyali ni joli sukaro kɔlɔsili la, o bɛ cogo kura di farikoloɲɛnajɛ banaw furakɛli ma.
Jaa 1 Maz ka kemikɛli cogoya.
Maz ka ɲɛfɔli kunbaba
Maz ye GLP-1/glucagon dual receptor agoniste ye, fura kura don farikoloɲɛnajɛ banaw furakɛli la. San tan damadɔ tɛmɛnenw na, furaw dilanni min ɲɛsinnen bɛ farikoloɲɛnajɛ banaw ma, o tora ka taa ɲɛ. GLP-1 minɛbaga agonistew ni glucagon minɛbaga agonistew ye furakɛli nɔ dɔw jira ni u kɛra u kelen na, nka u dan fana bɛ u yɛrɛ la. Walasa ka furakɛli suguya ɲuman ɲini, ɲininikɛlaw y’u sinsin furaw dilanni kan minnu bɛ se ka baara kɛ laɲini caman kan waati kelen na, o bɛ na ni Maz dabɔli ye. A yiriwali taabolo ye sɛgɛsɛgɛli gɛlɛnw kɛ ka kɔn kɛnɛyaso ɲɛ ani kɛnɛyaso sɛgɛsɛgɛli caman kɛra, ka a lakanani n’a nafa jira dɔɔnin dɔɔnin.
Fɛɛrɛ min bɛ Kɛ ni wale ye
(1) GLP-1 Recepteur (GLP-1 Recepteur) ka baarakɛcogo
Joli sukaro homeostasis ɲɛnabɔli : GLP-1 ye pepitiri ɔrimɔni ye min bɛ bɔ banakɔtaa L selilɛriw fɛ. GLP-1 minɛbaga baara kɔfɛ, Maz bɛ joli sukaro labɛn sira caman fɛ. A bɛ inisɔndiya bɔli sabati pankreyasi β selilɛriw fɛ, ka inisɔndiya kɛcogo ɲɛ, o la, a bɛ sukaro tali ni a baara teliya, ani ka sukaro hakɛ dɔgɔya joli la. A bɛ sukaro bɔli bali ka bɔ pankreyasi α selilɛriw la ani ka sugunɛ sukaro bɔli dɔgɔya, o bɛ joli sukaro sabatili sabati ka taa a fɛ.
Kɔnɔbara lankolonya bilali kɔfɛ : Maz bɛ GLP-1 minɛbaga baara, a bɛ baara kɛ kɔnɔbara basigilen na walasa ka kɔnɔbara lankolonya sumaya. O bɛ dumuni marali janya kɔnɔbara la, ka dɔ fara fasa kan ani ka dumuni dunta dɔgɔya, o bɛ kɛ sababu ye ka mɔgɔ girinya kunbɛn.
Dumuni nege labɛnni : GLP-1 minɛbaga baarakɛli kɔfɛ, taamasiɲɛw bɛ lase farikolo cɛmancɛ la, ka baara kɛ hipotalamu baloyɔrɔ la walasa ka dumuni nege bɛ tali kɛ farikolojidɛsɛbanakisɛw bɔli la, i n’a fɔ ka neuropeptide Y (NPY) jirali dɔgɔya ani ka dɔ fara proopiomelanocortin (POMC) jirali kan, o bɛ kɛ sababu ye ka fasa dusukunnata bila mɔgɔ la ani ka dumuni dunta dɔgɔya.
(2) Glucagon minɛbagaw ka baara
Fanga musaka sabatili : Ni sukaro minɛbaga bɛ baara kɛ Maz fɛ, o bɛ tulumafɛnw tiɲɛni ni asidi tulumafɛnw oksidan sabati, o bɛ dɔ fara fanga musaka kan. Ka fara o kan, a bɛ uncoupling protein 1 (UCP1) jiracogo kɔrɔta, ka funteni sɔrɔli sabati tulumafɛnw na, ka farikolo fanga sɛnɛcogo ɲɛ ka taa a fɛ ani ka dɛmɛ don farikolo girinya dɔgɔyali la.
Glucose metabolisme (Glucose metabolisme) ɲɛnabɔli : Glucagon minɛbagaw ka baarakɛcogo bɛ sugunɛbilenni ni gluconeogenesis (gluconeogenesis) sabati. Nka, Maz ka fanga kɔrɔ, o ɲɛtaa nɔ in tɛ joli sukaro hakɛ kɔrɔta dɔrɔn, nka o nɔ na, a bɛ joli sukaro labɛnni tigitigi sɔrɔ jɛɲɔgɔnya fɛ ni GLP-1 minɛbagaw ka baarakɛcogo ye. Ni sukaro hakɛ ka ca joli la, sukarodunbana nɔ min bɛ sɔrɔ GLP-1 minɛbagaw ka baarakɛcogo fɛ, o de ka ca; ni sukaro hakɛ dɔgɔyara joli la, sukarodunbana nɔ min bɛ sɔrɔ sukaro minɛbagaw ka baarakɛcogo fɛ, o bɛ sukarodunbana bali.
(3) Fɛɛrɛ min bɛ baara kɛ ɲɔgɔn fɛ
Maz bɛ GLP-1 minɛbagaw ni glucagon minɛbagaw bɛɛ baara waati kelen na. Siginiden sira minnu bɛ baara kɛ nin fɛn fila ninnu fɛ, olu bɛ baara kɛ ɲɔgɔn fɛ walasa ka farikoloɲɛnajɛ ɲɛnabɔli nɔba dɔ kɛ min ka bon kosɛbɛ ani min fanga ka bon. Kisɛya siratigɛ la, GLP-1 minɛbaga baarakɛli bɛ dɔ bɔ fanga sɔrɔli la ni dumuni nege dabila ye ani ka kɔnɔbara lankolonya bila kɔfɛ, ka sɔrɔ sukaro minɛbaga baarakɛli bɛ fanga musaka sabati. Fɛnɲɛnɛma fila bɛɛ ka jɛ-ka-baara bɛ kɛ sababu ye ka girinya dɔgɔya ka ɲɛ. Joli sukaro labɛnni siratigɛ la, a minɛbagaw ka baarakɛcogo fila bɛɛ nɔ bɛ ɲɔgɔn dafa walasa ka joli sukaro to a cogo la ani ka a yɛrɛ tanga fɛn caman jiginni ma.
3. Farikoloɲɛnajɛ nɔfɛkow
(1) A bɛ nɔ minnu bila mɔgɔ farikolo girinya dɔgɔyali la
Dɔgɔtɔrɔso daliluw : Dɔgɔtɔrɔso sɛgɛsɛgɛli caman y’a jira ko Maz bɛ mɔgɔ farikolo girinya dɔgɔyali nɔba bila. Kalan minnu kɛra ka balikuw kɛ minnu girinya ka ca walima minnu fasalen don san , dɔgɔkun 24 Maz furakɛli (ni a tata hakɛ cayalenba ye miligaramu 6 ye) o kɛra sababu ye ka mɔgɔ girinya dɔgɔya 6,7%–11,3%, ka sɔrɔ furakisɛ kulu ye 1,0% girinya sɔrɔ. A tata hakɛ kulu danfaralenw cɛma, Maz miligaramu 4,5 ni miligaramu 6 ye farikolo girinya dɔgɔyali nɔ jira ka caya, ni furakɛli danfara ni furakisɛ ta kɛra -7,7% na ka se -12,3% ma (P < 0,0001). Seginkanni sigilen ni meta-sɛgɛsɛgɛli la min kɛra ni mɔgɔ 680 ye, Maz ye nafa caman jira ka tɛmɛ furakisɛ kan farikolo girinya dɔgɔyali la, ni danfara hakɛ (MD) ye -6,22% ye (95% dannaya hakɛ [CI]: -8,02% ka se -4,41%).
Jaa 2 Farikolo girinya nafa labanyɔrɔw. a Yɛlɛma kɛmɛsarada la ka bɔ a daminɛ na farikolo girinya la dɔgɔkun 24. b Yɛlɛma kɛmɛsarada la ka bɔ a daminɛ na farikolo girinya la waati kɔnɔ.
(2) Glycémique régulation nɔ minnu bɛ sɔrɔ
A bɛ nɔ minnu bila banabagatɔw la minnu ka farikoloɲɛnajɛ suguya 2 bɛ u la: Banabagatɔ minnu ka farikoloɲɛnajɛ suguya 2 bɛ u la, Maz bɛ dɔ bɔ kosɛbɛ ɛmoɲini A1c (HbA1c) ni sunɔgɔ la joli sukaro hakɛ la. Fase 2 kɛnɛyako sɛgɛsɛgɛli dɔ la min kɛra ni mɔgɔw ye, min kɛra ni mɔgɔ fila ye, min kɛra ni furakisɛ ye, banabagatɔ minnu farikolojidɛsɛ suguya 2 bɛ u la, minnu ye Maz furakɛli kɛ (ni a tata hakɛ cayalenba ye miligaramu 6 ye) dɔgɔkun 20 kɔnɔ, olu ye yeli kɛ HbA1c hakɛ cayalenba la min bɛ daminɛ -1,41% na ka se -1,67% ma, ka sɔrɔ furakisɛ kulu ye fɛn dɔ yeli jira ni 0,03% ye, ni danfaraba bɛ u ni ɲɔgɔn cɛ jateminɛ na furakisɛ tali (P < 0,0001). Banabagatɔw fana ye dɔ bɔ kosɛbɛ farikolo girinya la, ni kɛmɛsarada la fɛn caman yeli ye jɛɲɔgɔnya jira min bɛ tali kɛ fura tata hakɛ la, o sera -7,1% ma.
Nafa minnu bɛ joli sukaro hakɛ labɛnni na : Maz tɛ joli sukaro hakɛ dɔgɔya dɔrɔn, nka a bɛ joli sukaro caman ɲɔgɔnnabɔli fana ɲɛ ani ka sukarodunbana kow farati dɔgɔya. Ni an y’a suma ni sukarodunbana furaw ye minnu bɛ kɛ ka caya, a ka baarakɛcogo min bɛ wele ko dual receptor agoniste, o bɛ se ka joli sukaro hakɛ jateminɛ tigitigi ani ka ɲɛ, o bɛ banabagatɔw ka ɲɛnamaya kɛcogo ɲɛ ani ka u ka ɲɛnamaya kuntaalajan ɲɛ.
(3) A bɛ nɔ minnu bila dusukun ni jolisiraw ni farikoloɲɛnajɛ taamasiɲɛw la
Tansiyɔn labɛnni : Maz bɛ tansiyɔn sistoliki ni tansiyɔn diastolic fila bɛɛ dɔgɔya. Seginkanni sigilenw ni meta-sɛgɛsɛgɛliw b’a jira ko ni i ye a suma ni furakisɛ ye, Maz bɛ tansiyɔn sistoliki dɔgɔya ni danfara ye (MD) min ye -7,57 mmHg ye (95% CI: -11,17 ka se -3,98 mmHg ma) ka ɲɛsin tansiyɔn jiginni ma diyastoliki fɛ, MD tun ye -2,98 mmHg ye (95% CI: -5,74 fo -0,22 mmHg). O bɛ se ka kɛ sababu ye ka Maz ka fɛɛrɛ caman sɔrɔ, i n’a fɔ ka joli siraw kɔnɔna baara ɲɛ, ka joli siraw laminiw kɛlɛli dɔgɔya, ani ka ji ni natiri balansi labɛn.
Lipid regulation : Maz bɛ lipid profiles labɛn ka ɲɛ. A bɛ kolosinsinnan bɛɛ lajɛlen dɔgɔya (MD = -16,82%, 95% CI: -24,52 ka se -9,13%), triglycérides (MD = -43,29%, 95% CI: -61,57 ka se -25,01%), ani lipoprotéines low-density (MD = -17,07%, 95% CI: -25,54 fo -8,60%). hakɛw la, ka sɔrɔ fana ka sariyasunba nɔ dɔ bila lipoprotéines hautes (MD = -7,54%, 95% CI: -11,26 fo -3,83%) la. O nɔ ninnu bɛ dɛmɛ ka dusukunnabana farati dɔgɔya ani ka nɔ bila dusukun ni jolisiraw lakanani na.
(4) A bɛ nɔ minnu bila jolidɛsɛ la
Baganw ka kɔrɔbɔli daliluw : Sosow ka misali sɛgɛsɛgɛli dɔ la, min kɛra sosow la, ni u pikiri kɛra farikolo jukɔrɔ miligaramu 0,05/kg ani miligaramu 0,075/kg Maz (tile 3 o tile 3) o ye asidi uriki (SUA) hakɛ dɔgɔya kosɛbɛ sosow la. Ni an ye a suma ni HUA kulu ye, SUA ni serum creatinine (SCr) hakɛ dɔgɔyara kosɛbɛ Maz-MD ni Maz-HD kuluw la, ani sugunɛbilenni (U-Pro) hakɛ fana dɔgɔyara kosɛbɛ Maz-MD kulu la. Ka fara o kan, Maz ye sugunɛbaralabana caman yeli ɲɛ HUA wuluw la.
Jaa 3 a: Yɛlɛma kɛmɛsarada la farikolo girinya la ka bɔ a daminɛ na waati kɔnɔ. b: Lajɛden minnu bɛ se ka girinya dɔgɔyali laɲiniw sɔrɔ, olu hakɛ.
Aplikasi Sɛgɛsɛgɛli
(1) Kɛnɛyaso ka sɛgɛsɛgɛliw ɲɛtaa
Kɛnɛyaso sɛgɛsɛgɛli fɔlɔw : Fasa 1 furakɛli sɛgɛsɛgɛli fɔlɔw ye Maz lakanani, a muɲuni ani a nafa fɔlɔ jateminɛ fɔlɔ. Fase 1b sɛgɛsɛgɛli dɔ la min kɛra ni mɔgɔw ye, min kɛra ni furakisɛ ye, ni a tata hakɛ caman bɛ kɛ ka caya Fase 1b, balikuw minnu girinya ka ca walima minnu fasalen don, olu ye Maz hakɛ danfaralenw di u ma (fo ka se miligaramu 10 ma). Jateminɛw y’a jira ko Maz tun bɛ muɲu kosɛbɛ nin hakɛ in kɔnɔ, ko kɔlɔlɔ jugu si ma fɔ, wa a girinya dɔgɔyara kosɛbɛ.
Fasa 2 kɛnɛyako sɛgɛsɛgɛli : Fasa 2 kɛnɛyaso sɛgɛsɛgɛli ye Maz nafa ni a lakanani sinsin ka taa a fɛ jamana suguya wɛrɛw la. Fasa 2 sɛgɛsɛgɛli dɔ la min kɛra Sinuwa banabagatɔw kan minnu ka farikoloɲɛnajɛ suguya 2 bɛ u la, Maz ye nɔba jira HbA1c ni farikolo girinya dɔgɔyali la, ni lakana bɛ se ka suma ni furakisɛ kulu ye. Kɔnɔnatumu minnu ka teli ka sɔrɔ, olu tun ye kɔnɔbara basigilenw ye minnu ka dɔgɔn fo ka se u danma ma, i n’a fɔ kɔnɔboli ni kɔnɔboli. Fasa 2 sɛgɛsɛgɛli la min kɛra balikuw kan minnu girinya ka ca walima minnu fasalen don, dɔgɔkun 24 Maz furakɛli (fo ka se miligaramu 6 ma) y’a jira ko farikolo girinya dɔgɔyali nafa ka bon ani ka a lakana.
(2) Kalan minnu bɛ kɛ ka fura wɛrɛw suma ɲɔgɔn na
Ni aw ye a suma ni GLP-1 minɛbagaw ye : Ni aw ye a suma ni laadala GLP-1 minɛbagaw ye, Maz bɛ se ka nɔba bila farikolo girinya dɔgɔyali la ani joli sukaro hakɛ labɛnni na ka a sababu kɛ a ka GLP-1 minɛbagaw ni sukaro minɛbagaw ka baara kɛ siɲɛ fila. Kalan dɔw la, Maz ye girinya dɔgɔya ka tɛmɛ GLP-1 minɛbaga dɔw kan furakɛli waati kelen kɔnɔ, wa a ye sabatili ɲuman jira joli sukaro kɔlɔsili la.
Ni aw ye a suma ni sukarodunbana fura wɛrɛw ye : Ni aw ye a suma ni laadala sukarodunbana furaw ye minnu bɛ ta da la, Maz tɛ joli sukaro dɔgɔya dɔrɔn, nka a bɛ nafa wɛrɛw fana di i n’a fɔ farikolo girinya dɔgɔyali ani dusukun ni jolisiraw ka farikoloɲɛnajɛ taamasiɲɛw ɲɛnabɔli.
Kuncɛli
I n’a fɔ GLP-1/glucagon dual receptor agonist, Maz bɛ fanga sɛnɛcogo, joli sukaro, tansiyɔn, ani joli tulumafɛnw labɛnni bɛɛ lajɛlen sɔrɔ, a kɛtɔ ka farikoloɲɛnajɛ ɲɛnabɔlan nafama fila baara waati kelen na, o bɛ furakɛli nɔ bɛɛ lajɛlen ni fangatigi jira ka tɛmɛ recepteur kelen agoniste kan. Maz bɛ layidu ɲuman ta farikoloɲɛnajɛ bana suguya caman na, i n’a fɔ fasa, farikolojɔli suguya 2, ani jolidɛsɛ.
Sosow (Sɔrɔyɔrɔw).
[1] Zhang B, Cheng Z, Chen J, ani mɔgɔ wɛrɛw. Maz nafa ni a lakanani Sinuwa banabagatɔw la minnu ka fɛnɲɛnamafagalan suguya 2 bɛ u la: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial[J]. Fɛnɲɛnɛmafagalanw ladonni, 2024,47(1):160-168.DOI:10.2337/dc23-1287.
[2] Nalisa D. L., Kuboia N., Dyab E., ani a ɲɔgɔnnaw. Maz ka nafa ni a lakanani farikolo girinya dɔgɔyali la sukarodunbanabagatɔw ni sukarodunbanabagatɔw tɛ minnu na: seginnkanni kɛcogo sigilen ani sɛgɛsɛgɛli kɛcogo kɔrɔlenw sɛgɛsɛgɛli kɛlenw kan[J]. Dancɛw ka ɲɛsin Endocrinologie ma, 2024,15. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.
[3] Ji L, Jiang H, Cheng Z, ani mɔgɔ wɛrɛw. Fasa 2nan mazdutidi sɛgɛsɛgɛli kɛcogo la min kɛra ni mɔgɔw ye, Sinuwa baliku minnu girinya ka ca walima mɔgɔkɔrɔbaw la minnu fasalen don[J]. Sigida ka kumaɲɔgɔnya, 2023,14(1):8289.DOI:10.1038/s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: Peptide-1 (GLP-1R) ani Glucagon (GCGR) minɛbaga kura min bɛ i n’a fɔ glucagon, Maz (IBI362), A bɛ Hyperuricemia dɔgɔya sosow la minnu ka hyperruricemie[J]. Fɛnɲɛnɛmafagalanw, 2023. https://api.semanticscholar.org/CorpusID:259452040. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew
[5] Ji L, Gao L, Jiang H, ani mɔgɔ wɛrɛw. GLP-1 ni glucagon receptor dual agonist mazdutide (IBI362) miligaramu 9 ni miligaramu 10 lakanani ni a nafa Sinuwa balikuw la minnu girinya ka ca walima minnu fasalen don: Kɔrɔbɔli min kɛra k’a sɔrɔ a ma kɛ cogo si la, min bɛ kɛ ni furakisɛ ye, min bɛ kɛ ni a tata hakɛ caman wulilen ye, a tata hakɛ 1b Dɔgɔtɔrɔso furakɛli, 2022,54:101691.DOI:10.1016/j.eclinm.2022.101691.
Fɛn min bɛ sɔrɔ ɲininiw dɔrɔn kama:
