▎ Survodutide ɲinini
Survodutide ka ɲininiw kɛcogo ye mun ye?
Farikoloɲɛnajɛ banaw cayalenba:
Ni ɲɛnamaya teliya teliyalen don ani dumunikɛcogo caman yeli, farikoloɲɛnajɛ banaw i n’a fɔ fasa, sukarodunbana suguya 2, ani sugunɛbilenni min tɛ dɔlɔ ye (NASH) kɛra diɲɛ foroba kɛnɛyako gɛlɛyaw ye. Misali la, sugunɛbilenni min bɛ sɔrɔ farikoloɲɛnajɛ fɛ (MAFLD) cayalenba bɛ tɛmɛ 30% kan, wa a fɔra ko san 2030 na, farikolojidɛsɛ min bɛ sɔrɔ farikolojidɛsɛ fɛ (MASH) bɛna kɛ sugunɛbilenni sababuba ye, o bɛna doniba da kɛnɛyako kan.
Dɔrɔgu minnu bɛ yen, olu dan ye:
GLP-1 laadala furaw bɛ dan dɔw sɔrɔ farikoloɲɛnajɛ banaw furakɛli la. Banabagatɔ dɔw fɛ, farikolojidɛsɛ nɔ tɛ u wasa, walima u bɛ se ka kɔnɔboli kɔlɔlɔw sɔrɔ. Ka fara o kan, u seko ka sugunɛ tulumafɛnw sɛnɛcogo ɲɛ, o dan ye, wa u muɲuni bɛ se ka bonya ni u tali kuntaalajan.
Nafa minnu bɛ Dual Agonists la:
I n’a fɔ glucagon-like peptide-1 receptor (GLP-1R) ani glucagon receptor (GCGR) ka agoniste fila, Survodutide bɛ se ka farikoloɲɛnajɛ labɛn ka bɔ yɔrɔ caman na. GLP-1R sira fɛ, a bɛ se ka dumuni nege bali, ka kɔnɔbara lankolonya bila kɔfɛ, ani ka inisɔndiya bɔli sabati walasa ka joli sukaro hakɛ dɔgɔya. GCGR sira fɛ, a bɛ se ka asidi fatɔw ka oksidan caya sugunɛ na, ka tulumafɛnw dalajɛli dɔgɔya, ka sugunɛbilenni ɲɛ ka ɲɛ, o bɛ furakɛli nɔ ɲumanw jira fasa, sukarodunbana ani sugunɛbanaw la baganw ka kɔlɔsiliw la.
Survodutide ka baarakɛcogo ye mun ye?
1. Agonisme (Agonisme) min bɛ wele ko Dual Receptor
Survodutide ye agoniste fila ye glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) la.
GLP-1R Agonisme (banakisɛfagalan).
GLP-1 minɛbaga baara kɔfɛ, a bɛ se ka inisɔndiya min bɛ tali kɛ sukaro la, o bonya ani ka sukaro bɔli bali, o la, a bɛ sukaro hakɛ dɔgɔya joli la. Ni Survovudutide ye GLP-1R baara, a bɛ se ka inisɔndiya bɔli sabati pankreyasi gun β selilɛriw fɛ ani o waati kelen na, ka sukaro bɔli dɔgɔya pankreyasi gun α selilɛriw fɛ, ka joli sukaro labɛnni ɲuman sɔrɔ.
Ka fara o kan, GLP-1R agoniste fana bɛ se ka kɔnɔbara lankolonya bila kɔfɛ ani ka dɔ fara fasa dusukunnata kan, o la, a bɛ dɛmɛ ka dumuni dunta dɔgɔya ani ka farikolo girinya kunbɛn.
GCGR Agonisme (Agonisme) ye
Glucagon minɛbaga baara bɛ se ka dɔ fara fanga ta kan ani ka tulumafɛnw tiɲɛni sabati. Survodutide bɛ GCGR lawuli, ka dɔ fara farikolo fanga falenfalen hakɛ kan ani ka triglycérides minnu bɛ tulumafɛnw na ka tila ka kɛ asidi tulumaw ni glycérol ye, o bɛ fanga sɔrɔyɔrɔ di farikolo ma.
2. A nɔ minnu bɛ sɔrɔ farikoloɲɛnajɛ la
Glucose metabolisme (Glucose) ka ɲɛtaa
Survovudutide bɛ dɔ bɔ kosɛbɛ ɛmoɲini (HbA1c) hakɛ la. Dɔgɔtɔrɔso ka sɛgɛsɛgɛliw la, sukarodunbana suguya 2 banabagatɔ minnu furakɛra ni Survovudutide ye, olu ye dɔ bɔ kosɛbɛ HbA1c hakɛ la furakɛli dɔgɔkun 16 kɔfɛ. Misali la, ni aw ye a suma ni semaglutide ye, Survovudutide (DG2) hakɛ dɔgɔmannin fana ye o nɔ kelen bila HbA1c dɔgɔyali la. HbA1c hakɛ DG2 kulu la, o dɔgɔyara ni miligaramu 15,95/mol/mol (-1,46%), ka sɔrɔ semaglutide kulu la, o dɔgɔyara ni miligaramu 16,07/mol (-1,47% ).
A kɛcogo bɛ se ka sɔrɔ ni inisɔndiya bɔli caya ye, ka sukaro bɔli bali, ani ka sukaro tali ni a baaracogo ɲɛ farikolo yɔrɔw fɛ.
Lipide metabolisme (Lipide metabolisme) labɛnni
Survovudutide bɛ se ka joli la tulumafɛnw hakɛ dɔgɔya. Banabagatɔ fasalenw ka sɛgɛsɛgɛli dɔ la, ni i ye a suma ni furakisɛ ta ye, Survodutide ye dɔ bɔ kosɛbɛ triglycéride (TG) hakɛ la, ani fana a ye dɔ bɔ lipoprotéines low-density (LDL), kolosinsinnan bɛɛ lajɛlen (TC), ani lipoprotéines non-high-density (non-HDL-C) hakɛ la fura tata hakɛ kulu dɔw la.
O waati kelen na, Survodutide bɛ se ka sugunɛ tulu hakɛ fana dɔgɔya. Sɛgɛsɛgɛli dɔ kɛra banabagatɔw kan minnu bɛ ni farikolojidɛsɛ ye (MASH), banabagatɔ minnu furakɛra ni Survovudutide ye, minnu ka sugunɛ tulu hakɛ dɔgɔyara ni 30% ye a dɔgɔyalenba la, o hakɛ tun ka ca kosɛbɛ ka tɛmɛ furakisɛ kulu ta kan. Misali la, banabagatɔ 63%, 67% ani 57% minnu bɛ Survovudutide miligaramu 2,4, miligaramu 4,8 ani miligaramu 6,0 kuluw la, olu sera nin taamasiɲɛ in ma, k’a sɔrɔ furakisɛ tali kuluw la, 14% dɔrɔn.
3. A nɔ minnu bɛ dusukun ni jolisiraw la
Dusukun ni jolisiraw ka faratiw ɲɛnabɔli
Survovudutide bɛ se ka tansiyɔn jigin. Banabagatɔ fasalenw na, ni aw ye a suma ni furakisɛ ta ye, tansiyɔn sistoliki (SBP) ni tansiyɔn diastoliki (DBP) fila bɛɛ dɔgɔyara kosɛbɛ furakɛli kɔfɛ ni Survodutide ye. Furakɛli yɛrɛ la, Survodutide bɛ se ka dɔ bɔ SBP la fo ka se milimɛtiri 10,2 ma ani ka DBP fo milimɛtɛrɛ 4,8, wa a tansiyɔn jiginni nɔ bɛ bɔ ɲɔgɔn na hali ni tansiyɔn jiginni tun bɛ banabagatɔ la sani a ka sɛgɛsɛgɛli kɛ dɔgɔya .
Ka fara o kan, Survodutide bɛ se ka cɛsirilan lamini fana dɔgɔya. Banabagatɔ fasalenw na, Survodutide tata hakɛ kulu bɛɛ la banabagatɔw cɛmancɛ laminiw dɔgɔyara, wa miligaramu 4,8 kulu de ye dɔgɔya hakɛ cayalenba sɔrɔ, o kɛra santimɛtɛrɛ 16,6 ye.
Stɛatohepatitis (NASH) min tɛ dɔlɔminna ye, o taamasiɲɛw nɔfɛkow .
Survovudutide bɛ se ka nɔ ɲuman bila sugunɛbilenni taamasiɲɛ dɔw la minnu tɛ dɔlɔ ye (NASH). Sisan sɛgɛsɛgɛliw y’a jira ko Survodutide bɛ se ka jɔyɔrɔba ta NASH yiriwali balili la ni a bɛ sugunɛ tulumafɛnw falenfalenni ni a funu cogoya ɲɛ.
Survodutide baarakɛcogo ye mun ye?
1. Jabɛti suguya 2 ni fasa furakɛli
I n’a fɔ agoniste fila min bɛ baara kɛ waati jan kɔnɔ, Survodutide bɛ kɛ siɲɛ kelen dɔgɔkun kɔnɔ, wa a ye nɔba jira sukarodunbana suguya 2 (T2DM) ni fasa furakɛli la.
Hémoglobine glycé (HbA1c) dɔgɔyali:
Kɛnɛyaso sɛgɛsɛgɛli caman y’a jira ko Survodutide bɛ se ka HbA1c hakɛ dɔgɔya kosɛbɛ banabagatɔw la. Misali la, T2DM banabagatɔw ka sɛgɛsɛgɛli la, dɔgɔkun 16 furakɛli kɔfɛ, HbA1c hakɛ dɔgɔyara fo ka se 1,7% ma [4] . HbA1c ye taamasiɲɛ nafama ye min bɛ joli sukaro kɔlɔsili kuntaalajan jira, wa a dɔgɔyali kɔrɔ ye ko banabagatɔ ka joli sukaro kɔlɔsili ɲɛnabɔra.
Kisɛya dɔgɔyali nafama:
T2DM ni fasa fila bɛɛ bɛ banabagatɔ minnu na, Survodutide bɛ se ka girinya dɔgɔya fo ka se 14,9% ma furakɛli dɔgɔkun 46 kɔnɔ [4] . Nin ye ɲɛtaa nafama ye banabagatɔw bolo minnu bɛ gɛlɛya sɔrɔ girinya caya fɛ min bɛ sɔrɔ tuma caman na sukarodunbana furaw fɛ minnu bɛ kɛ ka caya. Kisɛya dɔgɔyali tɛ banabagatɔ ɲɛda cogoya ni a ka ɲɛnamaya kɛcogo ɲɛ dɔrɔn, nka a bɛ dɔ bɔ gɛlɛyaw fana na i n’a fɔ dusukunnabana.
2. Dusukun ni jolisiraw ka faratiw ɲɛnabɔli
Survodutide fana bɛ nɔ ɲuman bila dusukun ni jolisiraw ka faratiw la.
Tansiyɔn jiginni:
Banabagatɔ fasalenw ka kɛnɛyako sɛgɛsɛgɛli la, ni aw ye a suma ni furakisɛ ta ye, Survodutide bɛ se ka tansiyɔn sistoliki dɔgɔya fo ka se milimɛtiri 10,2 ma ani tansiyɔn diyastoliki fo ka se milimɛtiri 4,8 ma [2] . Tansiyɔn dɔgɔyali nafa ka bon kosɛbɛ dusukunnabana kunbɛnni na, kɛrɛnkɛrɛnnenya la banabagatɔw ma minnu ka fasa ni tansiyɔn jiginni fila bɛɛ bɛ u la.
Joli tulumafɛnw hakɛ ɲɛnabɔli:
Survodutide bɛ se ka triglycéride (TG) hakɛ dɔgɔya ani fana a bɛ nɔ dɔ bila joli tulumafɛnw hakɛ la i n’a fɔ lipoprotéines hautes (HDL), lipoprotéines low-densité (LDL), kolosinsinnan bɛɛ lajɛlen (TC), ani kolosinsinnan minnu tɛ HDL- ye C Misali la, furakɛli bolodalen na, TG hakɛ dantɛmɛnen Survodutide kuluw bɛɛ la, o dɔgɔyara kosɛbɛ.
3. Stɛatohepatitis (NASH) min tɛ dɔlɔ ye (NASH) furakɛli .
Survodutide fana bɛ se ka kɛ sababu ye ka sugunɛbilenni min tɛ dɔlɔ ye (NASH) furakɛli la.
Sugunɛbilenniw ka ɲɛtaa:
Dɔgɔkun 48 kɔnɔ, fasa 2nan na, banabagatɔ balikuw ka kɛnɛyako sɛgɛsɛgɛli la, minnu kɛra ni MASH (stéatohepatitis associée par métabolique) ani sugunɛbilenni ye, Survodutide tun ka fisa ni furakisɛ ye MASH ɲɛnabɔli la, k’a sɔrɔ a ma sugunɛbilenni juguya. Kɛrɛnkɛrɛnnenya la, banabagatɔ minnu furakɛra ni Survodutide hakɛ danfaralenw ye, banabagatɔ 47% minnu bɛ miligaramu 2,4 kulu la, banabagatɔ 62% minnu bɛ miligaramu 4,8 kulu la, ani banabagatɔ 43% minnu bɛ miligaramu 6,0 kulu la, olu ye ɲɛtaa jira MASH la, ka sɔrɔ 14% dɔrɔn de ye furakisɛ ta kulu la.
Sugunɛbilenni tulu hakɛ dɔgɔyali:
Survodutide fana bɛ se ka sugunɛ tulu hakɛ dɔgɔya. Kɛnɛyako sɛgɛsɛgɛli min kofɔra sanfɛ, banabagatɔ 63%, 67% ani 57% minnu furakɛra ni Survodutide miligaramu 2,4, miligaramu 4,8 ani miligaramu 6,0 ye, olu ka sugunɛ tulu hakɛ dɔgɔyara ni 30% ye a dɔgɔyalenba la, k’a sɔrɔ furakisɛ tali kulu la, 14% dɔrɔn.
Sugunɛbilenni ɲɛnabɔli:
Ka fara o kan, a ye sugunɛbilenni ɲɛ fo ka se hakɛ dɔ ma. Nin sɛgɛsɛgɛli in na, banabagatɔ 34%, 36% ani 34% minnu furakɛra ni Survodutide miligaramu 2,4, miligaramu 4,8 ani miligaramu 6,0 ye, olu ye sugunɛbilenni ɲɛtaa jira fo ka se taamasiɲɛ kelen ma, k’a sɔrɔ a kɛra 22% ye furakisɛ kulu la.
4. Dumuni duntaw nɔfɛkow ni jolidɛsɛ furakɛli
Hamster fasalenw ka misali la, Survodutide ni fura wɛrɛ, Semaglutid, fila bɛɛ bɛ se ka kɛ sababu ye ka mɔgɔ girinya dɔgɔya ani ka insuline resistance index (HOMA-IR) dɔgɔya, nka u nɔ tɛ kelen ye dumuni diyabɔli ni jolidɛsɛ la.
Dumuni dunta nɔ min bɛ sɔrɔ:
Semaglutidi ye dɔ bɔ kosɛbɛ balo basigilenw ni balo tulumafɛnw dunni na furakɛli dɔgɔkun fɔlɔ la nka o kɔfɛ, a seginna a daminɛ na. O waati kelen na, a ye dɔ fara ji nɔgɔman dunni kan kosɛbɛ ani ka dɔ bɔ ji min falen bɛ fruktose la. O ni Survodutide ta tɛ kelen ye, Survodutide ma dumuni basigilen ni ji nɔgɔman dunni Changé nka a ye dɔ bɔ kosɛbɛ balo tulumafɛnw dunni na ani ji min falen don fructose la dɔgɔkun 5 furakɛli waati kɔnɔ.
A nɔ bɛ joli tulumafɛnw na:
Semaglutid ni Survodutide fila bɛɛ bɛ se ka joli la kolosinsinnan bɛɛ hakɛ dɔgɔya kosɛbɛ, ni a bɛ dɔgɔya ni 24% ni 41% ye. Semaglutid ka kolosinsinnan bɛɛ hakɛ dɔgɔyali kɛra sababu ye ka kolosinsinnanw hakɛ dɔgɔya ni 25% ye, nka kolosinsinnanw hakɛ dɔgɔyalen ma Changé. Survodutide ka kolosinsinnanw dɔgɔyali nɔ kɔlɔsira tulumafɛnw bɛɛ la, o la, jolisegindumuni kolosinsinnan minnu ka dɔgɔn, olu dɔgɔyara ni 39% ye [5] ..
Kuncɛli la, i n’a fɔ Survodutide min bɛ se ka farikoloɲɛnajɛ kɛcogo ɲɛnabɔ, ka joli sukaro dɔgɔya, ka farikolo girinya dɔgɔya, ka dusukun ni jolisiraw faratiw ɲɛ, ani ka sugunɛbilenni taamasiɲɛw ɲɛ, minnu tɛ dɔlɔ ye. A bɛ hakilina kuraw di banaw furakɛli kan minnu bɛ tali kɛ ɲɔgɔn na, wa a nafa ka bon kosɛbɛ banabagatɔw ka kɛnɛya sabatili la.
A sɛbɛnbaga ko la
Fɛn minnu kofɔlen dòn san fɛ, olu bɛɛ ɲinini Kɛra, k’u Labɛn ani k’u Lajɛ Cocer Peptides fɛ.
Dɔnniya gafe sɛbɛnbaga
Le Roux C ye ɲininikɛla ye min ni jɛkulu damadɔ bɛ ɲɔgɔn na. Olu ye Dublin Iniwɛrisite Kolɛji, St Vincents Uni Hosp, Ulster Iniwɛrisite, Saint Vincent ka Iniwɛrisite dɔgɔtɔrɔso, St Vincents Hosp Grp, KU Leuven, Iniwɛrisite dɔgɔtɔrɔso Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, Göteborg Iniwɛrisite, Imperial Kolɛji Lɔnduru, ICL, Univ Dublin, Istituto per la Sintesi Organica e la Fotoreattivita (ISOF-CNR), Maastricht Iniwɛrisite, King’s College dɔgɔtɔrɔso, King’s College dɔgɔtɔrɔso NHS Foundation Trust, Musgrove Park dɔgɔtɔrɔso ani Fasokanw ka dɔgɔtɔrɔso min ɲɛsinnen bɛ hakili ni hakililabaara ma.
A ka ɲininiw nafa ka bon - a bɛ tali kɛ Opereli, Endocrinology & Metabolism, Nutrition & Dietetics, Oncology, ani Biochimistry & Molecular Biology. A ka baara minnu Kɛra o ko ninnu na, olu b’a ka dɔnniyaba Jira ani a ye dɛmɛba minnu Kɛ furakɛli dɔnniya yiriwali la. Le Roux C tɔgɔ sɛbɛnnen bɛ citation (citation) ɲɛfɔli sɛbɛn kɔnɔ [2].
