▎ Nnyocha Survodutide
Kedu ihe ndabere nyocha nke Survodutide?
Mgbasa nke Ọrịa Metabolic:
Site n'ịkwalite ngwa ngwa nke ndụ na mgbanwe usoro ihe oriri, ọrịa metabolic dị ka oke ibu, ụdị 2 ọrịa shuga mellitus, na steatohepatitis na-adịghị egbu egbu (NASH) aghọwo ihe ịma aka ahụike ọha na eze zuru ụwa ọnụ. Dịka ọmụmaatụ, ọnụ ọgụgụ nke ọrịa imeju na-ejikọta metabolic na-emetụta abụba abụba (MAFLD) karịrị 30%, a na-ebukwa amụma na site na 2030, steatohepatitis metabolic dysfunction-associated steatohepatitis (MASH) ga-abụ isi ihe kpatara ntụgharị imeju, na-etinye nnukwu ibu na usoro nlekọta ahụike.
Mmachi nke ọgwụ ndị dị adị:
Ọgwụ GLP-1 ọdịnala nwere oke ụfọdụ na ọgwụgwọ ọrịa metabolic. Maka ụfọdụ ndị ọrịa, mmetụta mbelata ibu adịghị enye afọ ojuju, ma ọ bụ na ha nwere ike ịnweta mmetụta nke eriri afọ. Ọzọkwa, ikike ha imeziwanye abụba abụba imeju nwere oke, na ndidi nwere ike ịmalite site na iji ogologo oge.
Uru nke Dual Agonists:
Dị ka agonist abụọ nke onye na-anabata glucagon-dị ka peptide-1 (GLP-1R) na onye na-anabata glucagon (GCGR), Survodutide nwere ike ịhazi metabolism site na ọtụtụ akụkụ. Site n'ụzọ GLP-1R, ọ nwere ike igbochi agụụ, igbu oge ịgbasa afọ, ma kwalite mmepụta insulin iji belata ọkwa glucose ọbara. Site na ụzọ GCGR, ọ nwere ike ịkwalite oxidation fatty acid na imeju, belata mkpokọta abụba, ma melite fibrosis imeju ozugbo, na-egosipụta mmetụta ọgwụgwọ dị mma na oke ibu, ọrịa shuga, na ọrịa imeju na nnwale anụmanụ.
Kedu ihe bụ usoro nke Survodutide?
1. Dual Nnabata Agonism
Survodutide bụ agonist abụọ nke glucagon receptor (GCGR)/glucagon-dị ka peptide-1 nnabata (GLP-1R).
GLP-1R Agonism
Mgbe ịgbalite onye na-anabata GLP-1, ọ nwere ike welie insulin na-adabere na glucose ma gbochie secretion glucagon, si otú ahụ belata ọkwa glucose ọbara. Mgbe Survovudutide na-arụ ọrụ GLP-1R, ọ nwere ike ịkwalite mmepụta insulin site na mkpụrụ ndụ beta nke pancreatic islet yana, n'otu oge ahụ, ibelata glucagon secretion site na mkpụrụ ndụ α nke pancreatic islet, na-enweta ezigbo nhazi nke glucose ọbara ..
Na mgbakwunye, GLP-1R agonism nwekwara ike igbu oge ịpụpụ afọ ime ma mee ka uche zuru oke, si otú a na-enyere aka ibelata oriri na ịchịkwa ibu ahụ.
GCGR Agonism
Ịgbalite onye na-anabata glucagon n'ọrụ nwere ike ịbawanye oriri ume ma kwalite ndakpọ abụba. Survodutide na-akpali GCGR, na-abawanye ọkwa nke ike nke anụ ahụ ma na-akpali mbelata nke triglycerides na adipose anụ ahụ n'ime acid fatty na glycerol, na-enye ike maka ahụ ..
2. Mmetụta na Metabolism
Mmelite nke Metabolism Glucose
Survovudutide na-ebelata nke ọma ọkwa haemoglobin glycated (HbA1c). N'ime ọmụmụ ụlọ ọgwụ, ụdị ọrịa shuga 2 nke ejiri Survovudutide na-agwọ ọrịa gosipụtara mbelata dị ukwuu na ọkwa HbA1c mgbe izu iri na isii gachara ọgwụgwọ. Dịka ọmụmaatụ, atụnyere semaglutide, obere dose Survovudutide (DG2) nwere mmetụta yiri nke ahụ na ibelata HbA1c. Ọkwa HbA1c na otu DG2 gbadara site na 15.95 mmol/mol (-1.46%), ebe nke ahụ n'ime otu semaglutide belatara site na 16.07 mmol/mol (-1.47%) [1]..
Enwere ike ime usoro ya site n'ịkwalite mmepụta insulin, igbochi secretion glucagon, na imeziwanye nnabata na ojiji nke glucose site na anụ ahụ dị n'akụkụ.
Iwu nke Lipid Metabolism
Survovudutide nwere ike ibelata ọkwa lipid ọbara. N'ime nyocha nke ndị ọrịa buru ibu, ma e jiri ya tụnyere placebo, Survodutide belatara ọkwa triglyceride (TG) nke ukwuu, ma belata ọkwa nke lipoprotein dị ala (LDL), mkpokọta cholesterol (TC), na cholesterol na-abụghị HDL-C) n'ụdị ụfọdụ [2]..
N'otu oge ahụ, Survodutide nwekwara ike ibelata ọdịnaya abụba imeju. N'ime nnyocha nke ndị ọrịa nwere ọrịa metabolic dysfunction-ssociated steatohepatitis (MASH), ọnụ ọgụgụ nke ndị ọrịa a na-emeso ya na Survovudutide bụ ndị abụba imeju na-ebelata ma ọ dịkarịa ala 30% dị elu karịa nke ahụ na placebo. Dịka ọmụmaatụ, 63%, 67%, na 57% nke ndị ọrịa nọ na Survovudutide 2.4mg, 4.8mg, na 6.0mg otu, n'otu n'otu, ruru ihe ngosi a, ebe naanị 14% nọ na placebo otu [3]..
3. Mmetụta na Sistemụ Cardiovascular
Mmelite nke ihe ize ndụ nke obi
Survovudutide nwere ike belata ọbara mgbali. N'ime ndị ọrịa buru ibu, ma e jiri ya tụnyere placebo, ma ọbara mgbali systolic (SBP) na ọbara diastolic (DBP) belatara nke ukwuu mgbe ọgwụgwọ Survodutide gasịrị. Na ọgwụgwọ n'ezie, Survodutide nwere ike belata SBP site na 10.2 mmHg na DBP site na 4.8 mmHg, na mmetụta mbelata ọbara mgbali yiri nke ahụ n'agbanyeghị ma onye ọrịa ahụ nwere ọbara mgbali elu tupu nyocha [2]..
Tụkwasị na nke ahụ, Survodutide nwekwara ike ibelata n'úkwù. N'ime ndị ọrịa buru ibu, okirikiri úkwù nke ndị ọrịa n'ime otu dose Survodutide niile belatara, yana otu 4.8mg nwere mbelata kachasị ukwuu, nke bụ 16.6 cm [2]..
Mmetụta na ihe nrịbama nke Steatohepatitis na-adịghị mmanya (NASH)
Survovudutide nwere ike inwe mmetụta dị mma na ụfọdụ ihe nrịbama nke steatohepatitis na-adịghị egbu egbu (NASH). Ọmụmụ ihe dị ugbu a na-egosi na Survodutide nwere ike ịrụ ọrụ n'ịgbochi mmepe nke NASH site na imeziwanye abụba abụba na imeju na ọnọdụ mkpali [4]..
Kedu ihe bụ ngwa nke Survodutide?
1. Ọgwụgwọ ụdị ọrịa shuga mellitus nke 2 na oke ibu
Dị ka agonist dual na-eme ogologo oge, a na-enye Survodutide otu ugboro n'izu wee gosipụta mmetụta dị ukwuu na ọgwụgwọ ụdị ọrịa shuga mellitus 2 (T2DM) na oke ibu.
Mbelata haemoglobin glycated (HbA1c):
Ọtụtụ nnwale ụlọ ọgwụ egosila na Survodutide nwere ike belata ọkwa HbA1c nke ọma na ndị ọrịa. Dịka ọmụmaatụ, na nyocha nke ndị ọrịa T2DM, mgbe izu iri na isii nke ọgwụgwọ gasịrị, ọkwa HbA1c belatara ruo 1.7% [4] . HbA1c bụ ihe dị mkpa na-egosipụta njikwa glucose ọbara na-adịte aka, na mbelata ya pụtara na emelitela njikwa glucose ọbara onye ọrịa.
Mbelata ịdị arọ dị mkpa:
Maka ndị ọrịa nwere ma T2DM na oke ibu, Survodutide nwere ike nweta oke ibu ruo 14.9% n'oge 46 izu ọgwụgwọ [4] . Nke a bụ ihe dị mkpa maka ndị ọrịa na-enwe nsogbu n'ihi oke ibu nke ọgwụ mgbochi ọrịa shuga ọdịnala na-akpata. Mbelata ibu ọ bụghị naanị na-enyere aka melite ọdịdị na ọdịdị ndụ onye ọrịa kamakwa ọ na-ebelata ohere nke nsogbu dị ka ọrịa obi.
2. Mmelite nke ihe ize ndụ nke obi
Survodutide nwekwara mmetụta dị mma na ihe ize ndụ nke obi.
Mbelata Ọbara Ọbara:
N'ime ule ụlọ ọgwụ nke ndị ọrịa buru ibu, ma e jiri ya tụnyere placebo, Survodutide nwere ike ibelata ọbara mgbali systolic ruo 10.2 mmHg na ọbara diastolic site na 4.8 mmHg [2] . Mbelata ọbara mgbali dị oke mkpa maka igbochi ọrịa obi, ọkachasị maka ndị ọrịa nwere oke ibu na ọbara mgbali elu.
Mmelite nke oke lipid ọbara:
Survodutide nwere ike ibelata ọkwa triglyceride (TG) ma nwee mmetụta dị mma na oke lipid ọbara dị ka lipoprotein dị elu (HDL), lipoprotein dị ala (LDL), mkpokọta cholesterol (TC), na cholesterol na-abụghị HDL-C) [2] . Dịka ọmụmaatụ, na ọgwụgwọ a haziri ahazi, nkezi TG na otu Survodutide niile belatara nke ukwuu.
3. Ọgwụgwọ Steatohepatitis anaghị aṅụ mmanya (NASH)
Survodutide na-egosikwa ikike na ọgwụgwọ steatohepatitis na-adịghị egbu egbu (NASH).
Mmelite nke akụkọ ihe mere eme imeju:
N'ime izu 48, usoro 2 nke ụlọ ọgwụ nke ndị okenye nwere MASH (metabolic dysfunction-ssociated steatohepatitis) na imeju fibrosis, Survodutide dị elu karịa placebo na-emeziwanye MASH n'emeghị ka fibrosis imeju dịkwuo njọ. Kpọmkwem, n'etiti ndị ọrịa na-agwọ ọrịa dị iche iche nke Survodutide, 47% nke ndị ọrịa na 2.4mg otu, 62% nke ndị ọrịa na 4.8mg otu, na 43% nke ndị ọrịa na 6.0mg otu gosiri ọganihu na MASH, ebe nanị 14% na placebo otu [3].
Mbelata ọdịnaya abụba imeju:
Survodutide nwekwara ike ibelata abụba imeju. N'ime nnwale ụlọ ọgwụ ahụ a kpọtụrụ aha n'elu, 63%, 67%, na 57% nke ndị ọrịa ejiri 2.4mg, 4.8mg, na 6.0mg nke Survodutide, n'otu n'otu, belatara abụba imeju ma ọ dịkarịa ala 30%, ebe naanị 14% nọ na placebo otu [3]..
Mmelite nke Fibrosis imeju:
Na mgbakwunye, ọ na-emeziwanye fibrosis imeju ruo n'ókè ụfọdụ. N'ime ule a, 34%, 36%, na 34% nke ndị ọrịa na-emeso 2.4mg, 4.8mg, na 6.0mg doses nke Survodutide, n'otu n'otu, gosipụtara mmụba na fibrosis imeju nke ọ dịkarịa ala otu ọkwa, ebe ọ bụ 22% na placebo otu [3]..
4. Mmetụta na Mmasị nri na Mmelite nke Dyslipidemia
N'ime ụdị hamster buru ibu, ma Survodutide na ọgwụ ọzọ, Semaglutid, nwere ike ibute mbelata ibu ma belata nguzogide insulin (HOMA-IR), mana ha nwere mmetụta dị iche iche na mmasị nri na dyslipidemia.
Mmetụta na oriri nri:
Semaglutid belatara nke ukwuu oriri nke nri mgbe niile na nri nwere abụba dị elu n'izu mbụ nke ọgwụgwọ mana emesia laghachi na uru ntọala. N'otu oge ahụ, ọ na-abawanye oriri nke mmiri nkịtị ma belata oriri nke fructose nwere mmiri. N'ụzọ dị iche, Survodutide agbanweghị oriri nke nri oge niile na mmiri nkịtị mana ọ belatara oriri nke nri nwere oke abụba na mmiri nwere fructose n'oge oge ọgwụgwọ izu 5 [5]..
Mmetụta na lipids ọbara:
Ma Semaglutid na Survodutide nwere ike belata ọkwa cholesterol mkpokọta plasma nke ukwuu, yana mbelata 24% na 41% n'otu n'otu. Mbelata mkpokọta cholesterol site na Semaglutid butere mbelata 25% na ọkwa lipoprotein cholesterol dị elu, mana ọkwa lipoprotein dị obere njupụta agbanwebeghị. Ahụrụ mmetụta mbelata cholesterol nke Survodutide na mpaghara lipoprotein niile, gụnyere mbelata 39% na cholesterol lipoprotein dị obere [5]..
N'ikpeazụ, dị ka agonist abụọ na-anabata ihe, Survodutide nwere ike ịhazi metabolism, belata glucose ọbara, belata ibu ahụ, meziwanye ihe ize ndụ nke obi, ma melite akara nke steatohepatitis na-abụghị mmanya. Ọ na-enye echiche ọhụrụ maka ọgwụgwọ ọrịa ndị metụtara ya ma dị oke mkpa maka ịkwalite ọkwa ahụike nke ndị ọrịa.
Banyere Onye dere ya
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Onye ode akwụkwọ akụkọ sayensị
Le Roux C bụ onye nyocha jikọtara ya na ọtụtụ ụlọ ọrụ. Ndị a gụnyere University College Dublin, St Vincents Uni Hosp, Ulster University, Saint Vincent's University Hospital, St Vincent Hosp Grp, KU Leuven, University Hospital Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, University of Gothenburg, Imperial College London, ICL, Univ Dublin, Istituto per e laSentre Foto Organica (Maa-Sinte Foto Organica). Mahadum, King's College Hospital, King's College Hospital NHS Foundation Trust, Musgrove Park Hospital na National Hospital for Neurology & Neurosurgery.
Mmasị nyocha ya dị obosara - dị iche iche, na-ekpuchi ịwa ahụ, Endocrinology & Metabolism, Nutrition & Dietetics, Oncology, na Biochemistry & Molecular Biology. Ọrụ ya na mpaghara ndị a na-egosipụta nkà ya dị ukwuu na ntinye aka dị ukwuu o nyeworo na ọganihu nke sayensị ahụike. Edepụtara Le Roux C na ntụnye aka nke ntụaka [2].
