By Cocer Peptides 
1 ọnwa gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
1. Okwu mmalite
Ibu ibu aghọwo nchegbu ahụike ọha na eze na-arịwanye elu n'ụwa nile, na-abawanye ohere nke nsogbu dị iche iche dị ka ọrịa obi na ọrịa shuga. Ịchọta ọgwụ ọgwụgwọ oke ibu dị irè dị oke mkpa. Survodutide, dị ka agonist dual na-arụ ọrụ na onye na-anabata glucagon (GCGR) na onye na-anabata glucagon-dị ka peptide-1 (GLP-1R), na-egosi ikike dị ukwuu na ngalaba ọgwụgwọ oke ibu.
Ọgụgụ 1 Mmetụta glucagon-dị ka peptide-1 (GLP-1), glucose-based insulinotropic polypeptide (GIP), na glucagon na akụkụ dị iche iche dị mkpa na anụ ahụ.
2. Nchịkọta nke Survodutide
2.1 ndabere mmepe
Ọnụ ọgụgụ zuru ụwa ọnụ nke oke ibu na ụdị ọrịa shuga mellitus 2 (T2DM) na-aga n'ihu na-arị elu, ọgwụ mgbochi ọrịa shuga na-ebutekarị ibu ibu, na-akpali mkpa ngwa ngwa maka ọgwụgwọ ọhụụ nke nwere ike ịgwọ T2DM n'otu oge na oke ibu. GLP-1 agonists receptor agonists (GLP-1 RAs) na dual GLP-1/GIP agonists egosila ịdị irè na ọnwụ dị arọ na mmụba nke metabolic, Survodutide (BI 456906) apụtawo dị ka onye na-ekwe nkwa, onye na-eme ogologo oge abụọ agonist ugbu a na-enyocha ya.
2.2 Usoro ebumnuche
Njirimara pụrụ iche nke Survodutide dabere na ikike ya ịmegharị GCGR na GLP-1R n'otu oge. GCGR na-achịkwa ọkwa glucose ọbara n'ụzọ bụ isi, na-akwalite glycogenolysis na gluconeogenesis n'ime imeju mgbe arụ ọrụ ya, si otú a na-ebuli ọkwa glucose ọbara. N'ime usoro ọrụ nke Survodutide, ọ bụghị naanị na-ebuli ọkwa glucose ọbara, kama ọ na-achịkwa metabolism ike site na imekọ ihe ọnụ na GLP-1R. A na-ekesa GLP-1R n'ọtụtụ anụ ahụ na akụkụ ahụ, gụnyere pancreas, eriri afọ, obi, na ụbụrụ. Ịrụ ọrụ GLP-1R na-akwalite mmepụta insulin, na-egbochi secretion glucagon, na-egbu oge ịwụsa afọ, na-abawanye satiety, si otú ahụ na-ebelata oriri oriri na ibelata ibu ahụ. Survodutide na-arụ ọrụ nchịkwa metabolic zuru oke site na agonism nke nnabata abụọ, na-enyere aka na ọgwụgwọ oke ibu.
3. Ọrụ Survodutide na ọgwụgwọ oke ibu
3.1 Mmetụta Iwu Ịdị arọ
Ọtụtụ ọmụmụ ụlọ ọgwụ egosila na Survodutide nwere mmetụta dị ukwuu na-ebelata ibu na ndị ọrịa buru ibu. N'ime ule ụlọ ọgwụ na-agba nke 2 na-elekwasị anya na ndị buru oke ibu na-enweghị ọrịa shuga, ndị sonyere 387 gbara afọ 18 ruo 75 nwere akara uka ahụ (BMI) ≥27 kg/m² E kenyere ya na otu ise na-enweghị usoro, na-anata injections subcutaneous kwa izu nke Survodutide (0.6, 2.4, 3.6, ma ọ bụ 4.8 mg) ma ọ bụ placebo maka izu 46. Na njedebe nke izu 46, ndị otu dose Survodutide niile gosipụtara oke ibu, yana otu 4.8 mg na-enweta mbelata ịdị arọ ruru 18.7%. Site na nyocha nke subgroup site na nwoke na nwanyị na BMI, ụmụ nwanyị gosipụtara ọkwa dị arọ karịa mgbe ha natachara 4.8 mg nke Survodutide, na nkezi arọ ọnwụ pasent nke -17.0%, ebe ụmụ nwoke nwere -11.9%. N'ime otu obere BMI dị iche iche, ndị sonyere na BMI <30 kg / m² onye natara ọgwụgwọ Survodutide 4.8 mg nwetara pasentị ọnwụ kachasị elu, na-eru -19.1%. Nke a na-egosi na Survodutide nwere mmetụta na-ebelata ibu na ndị ọrịa buru ibu nke ụdị nwoke na nwanyị dị iche iche na ọkwa BMI, yana mmetụta ndị ọzọ na-apụta na ụfọdụ obere obere.
Ọgụgụ 2 Isi ngwụcha ngwụcha nke izu 48 nke ọgwụgwọ akwadoro.
3.2 Mmetụta na nkesa abụba anụ ahụ
Na mgbakwunye na mkpokọta oke ibu, Survodutide nwekwara mmetụta bara uru na nkesa abụba anụ ahụ. E jiri ya tụnyere ndị otu placebo, ndị otu dose Survodutide niile gosipụtara mbelata gburugburu úkwù, yana otu 4.8 mg na-enweta mbelata kacha elu nke 16.6 cm. Mbelata gburugburu úkwù na-egosi mbelata nke abụba afọ, nke jikọtara ya na ihe ize ndụ nke ọrịa obi. Nke a na-egosi na ọ bụghị naanị na Survodutide na-ebelata ibu ahụ kamakwa na-eme ka nkesa abụba dị mma site na ibelata abụba afọ, si otú a na-ebelata ohere nke ọrịa obi na-emetụta oke ibu.
3.3 Mmelite na paramita metabolic
Survodutide abụghị naanị na-achịkwa ibu ahụ kamakwa ọ na-enwe mmetụta dị mma na ọtụtụ paramita metabolic. N'ihe banyere metabolism lipid, n'oge ọgwụgwọ, triglycerides (TG) belatara nke ukwuu n'ime otu Survodutide niile, yana lipoprotein dị obere (VLDL) belatara ntakịrị na otu ọgwụ Survodutide niile. LDL belatara na otu dose nke 2.4 na 3.6 mg, ebe mkpokọta cholesterol (TC) na cholesterol na-abụghị HDL (na-abụghị HDL-C) belatara na otu 0.6, 2.4, na 3.6 mg. HDL ka kwụsiri ike n'oge ọgwụgwọ niile. Banyere ọbara mgbali elu, na ọgwụgwọ n'ezie, Survodutide nwere ike ibelata ọbara mgbali systolic (SBP) ruo 10.2 mmHg na ọbara mgbali elu diastolic (DBP) site na 4.8 mmHg, na-enwe mmetụta ọbara mgbali elu yiri nke a na-ahụ n'agbanyeghị ma ọbara mgbali elu dị tupu nyocha. Mgbanwe ndị a na usoro metabolic na-enyere aka belata ihe ize ndụ nke ọrịa obi na ndị ọrịa buru ibu, na-egosipụtakwa uru Survodutide zuru oke na ọgwụgwọ oke ibu.
3.4 Usoro nke Omume
Survodutide na-egosipụta mmetụta mbelata ibu ya site na ịgbalite GCGR na GLP-1R. Ịgbalite GLP-1R na-akwalite mmepụta insulin, na-eme ka mmetụta insulin dịkwuo elu, na-ebelata agụụ, ma na-ebelata oriri. Ọ na-egbu oge ịpụpụ afọ, na-agbatị oge nri na-adị n'ime afọ ma na-abawanye satiety. Ntinye nke GCGR na-ekere òkè na nhazi usoro metabolic hepatic site na ịkwalite oxidation abụba na igbochi njikọ abụba, si otú ahụ belata mkpokọta abụba n'ime ahụ. Survodutide nwekwara ike imetụta metabolism ike na ịdị arọ ahụ site na usoro ndị na-apụtaghị ìhè dị ka ịhazi microbiota gut.
4. Ngwa nke Survodutide na ọgwụgwọ oke ibu
4.1 Ihe akaebe nyocha ụlọ ọgwụ
N'ime nyocha nke ndị ọrịa nwere ụdị ọrịa shuga 2 na oke ibu, Survodutide gosikwara ezigbo hypoglycemic na mmetụta mbelata ibu. Mgbe izu iri na isii nke ọgwụgwọ gasịrị, ọkwa hemoglobin A1c (HbA1c) nke ndị ọrịa belatara nke ukwuu, yana mbelata kachasị nke 1.7%, ịdị arọ ahụ gbadarakwara nke ukwuu, yana mbelata kachasị nke 14.9%. N'ime nnyocha nke ndị ọrịa nwere ọrịa metabolic dysfunction-metụtara steatohepatitis (MASH) na oke ibu, Survodutide ọ bụghị nanị na-emeziwanye ihe nrịbama akụkọ ihe mere eme imeju kamakwa butere ibu ibu na ndị ọrịa. Ọmụmụ ihe ndị a na-akwadokwa ịdị irè nke Survodutide n'ime ndị mmadụ dị iche iche nwere ọnọdụ oke ibu.
4.2 Uru atụnyere ọgwụ ndị ọzọ
Tụnyere ọgwụ ọdịnala na-ebelata ibu arọ, Survodutide na-enye ọtụtụ uru. Ọgwụ ndị na-ebelata ịdị arọ nke ọdịnala na-elekwasịkarị anya n'otu usoro, na-ebute oke arụmọrụ yana nnukwu ihe ize ndụ nke mmetụta ọjọọ. Otú ọ dị, Survodutide na-eme ihe site na nhụjuanya nke ndị na-anabata ya, na-ebelata ịdị arọ ahụ nke ọma ma na-eme ka usoro metabolic dị ka glucose ọbara, ọkwa lipid, na ọbara mgbali elu, si otú a na-enye mgbochi na ọgwụgwọ zuru oke maka nsogbu ndị metụtara oke ibu.
E jiri ya tụnyere ọgwụ ndị ọzọ na-ebelata ibu dị ka semaglutide (GLP-1 agonist receptor), na nnwale anụmanụ, ma Survodutide na semaglutide butere mbelata ibu. Agbanyeghị, Survodutide gosipụtara mmetụta pụrụ iche karịa na mmasị nri na adịghị mma nke lipid. Semaglutid na-ebelata oriri na mmalite nke ọgwụgwọ mana ọ na-alaghachi na ọkwa ntọala mgbe e mesịrị, ebe Survodutide na-ebelata oriri nke oke abụba na mmiri fructose dị elu n'ime oge ọgwụgwọ 5 izu. Banyere profaịlụ lipid, Semaglutid na-ebelata mkpokọta cholesterol site na ibelata HDL-cholesterol, ebe Survodutide na-egosi mbelata cholesterol n'ofe akụkụ lipoprotein niile, gụnyere LDL-cholesterol. Nke a na-egosi na Survodutide nwere ike inye mmetụta dị elu n'ịhazi oriri nri na profaịlụ lipid.
5. Nkwubi okwu
Survodutide, dị ka onye agonist dual novel nke GCGR/GLP-1R, na-egosipụta nrụpụta dị ukwuu na ọgwụgwọ oke ibu. Ọ bụghị naanị na ọ na-ebelata ibu ahụ nke ọma ma na-eme ka nkesa abụba dị mma ma na-achịkwa ọtụtụ usoro metabolic dị ka glucose ọbara, lipids ọbara na ọbara mgbali, na-enye ọtụtụ uru maka ndị ọrịa nwere oke ibu.
Isi mmalite
[1] Yousif A, Hassan E, Mudarres MF, et al. Survodutide, ọhụụ ọhụrụ na ọgwụgwọ oke ibu na ụdị ọrịa shuga mellitus 2: nyocha akụkọ [J]. Akwụkwọ akụkọ Yemen nke Medicine, 2024,3: 97-101.DOI: 10.18231 / j.yjom.2024.005.
[2] Le Roux CW, Steen O, Lucas KJ, et al. 6926 Subgroup Analysis by Gender and Body Mass Index (BMI) na ndị mmadụ bi na oke ibu/oke ibu na Survodutide, Glucagon/GLP-1 Nnabata Dual Agonist, Phase II Trial[J]. Akwụkwọ akụkọ nke Endocrine Society, 2024,8 (Mgbakwunye_1): bvae133-bvae163.DOI:10.1210/jendso/bvae163.033.
[3] Sanyal AJ, Bedossa P, Fraessdorf M, et al. Ọnwụnwa nke Survodutide na MASH na Fibrosis.[J]. Akwụkwọ akụkọ New England Journal of Medicine, 2024.
[4] Briand F, Augustin R, Bleymehl K, et al. 7279 Survodutide na Semaglutid Ha abụọ na-ebute Mbelata ibu ma gosi mmetụta dị iche iche na mmasị nri na Dyslipidemia na Nhọrọ Nri n'efu na-akpata Obese Hamster Model [J]. Akwụkwọ akụkọ nke Endocrine Society, 2024,8 (Mgbakwunye_1): bvae134-bvae163.DOI:10.1210/jendso/bvae163.034.
[5] Ya MBU, Rosenstock J, Hoefler J, et al. Mmetụta nzaghachi dose na HbA1c na mbelata ahụ nke survodutide, onye na-anabata glucagon/GLP-1, ma e jiri ya tụnyere placebo na semaglutide mepere emepe na ndị nwere ụdị ọrịa shuga 2: nnwale ụlọ ọgwụ na-enweghị usoro [J]. Diabetologia, 2023,67:470-482.
Ngwaahịa dị maka naanị nyocha:
