Semaglutid 10 mg

▎ Semaglutid Structure

▎ Semaglutid Research

Kedu ihe ndabere nyocha nke Semaglutid?

Semaglutid bụ glucagon mmadụ dị ka peptide-1 (GLP-1), nkewapụtara dị ka agonist nnabata GLP-1. GLP-1 bụ homonụ ebumpụta ụwa nke mkpụrụ ndụ eriri afọ na-ezobere mgbe o richara nri. Ọ na-ekere òkè n'ịkwalite mmepụta insulin na igbochi secretion glucagon, si otú ahụ na-achịkwa ọkwa glucose ọbara. Mmepe nke Semaglutid sitere na nyocha miri emi nke ọrụ physiological nke GLP-1. Otú ọ dị, GLP-1 nwere ọkara ndụ dị mkpụmkpụ dị mkpirikpi n'ime ahụ, na-adịru nanị ihe dị ka nkeji 1 ruo 2, nke a na-ekwu na ọ nwere ike imebi ya site na dipeptidyl peptidase-4 (DPP-4) enzymes n'ime ahụ. Iji merie mmachi a, ndị ọkà mmụta sayensị gbanwere nhazi nke GLP-1 site na ngbanwe amino acid dị iche iche na mgbakwunye nke otu nchebe, na-eme ka nguzogide ya na enzymes DPP-4 ma si otú a na-agbatị ogologo oge ọrụ ^[1] . Na nhazi nke Semaglutid, alanine na 8th na-anọchi anya α-aminoisobutyric acid (Aib). Mgbanwe a abụghị naanị na-eme ka nkwụsi ike nke ọgwụ ahụ dịkwuo mma kamakwa ọ na-ewusi njikọ ya na onye na-anabata GLP-1 (Ma H, 2020). Na mgbakwunye, eriri acid fatty pụrụ iche jikọtara ya na C-terminus, jikọtara site na γ-glutamine na residu lysine, na-agbatịkwu ọkara ndụ, na-eme ka ịgba ọgwụ mgbochi otu ugboro kwa izu ma ọ bụ nchịkwa ọnụ otu ụbọchị ^[1] . Na mbụ dabere na nyocha na mgbanwe nke GLP-1 eke, Semaglutid na-achọ ịnye nhọrọ ọgwụgwọ dị irè maka ndị ọrịa nwere ụdị 2 metabolism ^[1,2] . Mgbe nkwalite nhazi ya gasịrị, ọ na-ejigide ọrụ physiological nke GLP-1 ebe ọ na-emeziwanye akụrụngwa ọgwụ ya, na-aghọ agonist GLP-1 dị mkpa na-eme ogologo oge. Nnyocha na mmepe nke Semaglutid dị oke mkpa maka ọgwụgwọ ụdị 2 metabolism, na-enye ndị ọrịa nhọrọ ọhụrụ. Site n'ịkwalite usoro ahụ, ọ na-emeri nsogbu nke obere ndụ nke GLP-1 dị mkpụmkpụ, na-eme ka nkwụsi ike nke ọgwụ na ogologo oge na-arụ ọrụ.

Gịnị bụ usoro nke Semaglutid?

Semaglutid bụ glucagon na-arụ ọrụ ogologo oge dị ka peptide-1 (GLP-1) agonist nnabata, na usoro ya bụ nke a:

Iwu Glucose Ọbara: Dị ka akwụkwọ akụkọ glucagon-dị ka peptide-1 agonist receptor (GLP-1RA), Semaglutid na-ebelata agụụ ndị ọrịa maka nri ma belata mmasị ha maka nri nwere oke abụba site na igbochi agụụ. Ọ na-ahazi ebe a na-eri nri na hypothalamus, na-ebelata iri nri, na-abawanye satiety, na-egbochi ịfụfụ gastric, na ibelata motility eriri afọ, si otú a na-enweta ihe mgbaru ọsọ nke ịbelata ibu. Mbelata ibu na-enyere aka melite nguzogide insulin ma na-achịkwa ọkwa glucose ọbara ^[3] (Kim HS, 2021). Semaglutid na-ebute oke ibu n'ime òké site n'ụzọ akwara nke kesara. Nnyocha egosiwo na Semaglutid na-arụ ọrụ ozugbo na mpaghara dịka ụbụrụ ụbụrụ, septal nucleus, na hypothalamus. Ọ bụ ezie na ọ naghị agafe ihe mgbochi ụbụrụ-ọbara, ọ na-emekọrịta ihe na ụbụrụ site na akụkụ okirikiri na mpaghara ụfọdụ dị nso na ventricles. Ọ na-akpalite ịgbalite c-Fos etiti na mpaghara ụbụrụ 10, gụnyere mpaghara azụ azụ nke Semaglutid na mpaghara nke abụọ lekwasịrị anya ozugbo na-enweghị mmekọrịta GLP-1R ozugbo, dị ka akụkụ parabrachial nucleus. Nyocha akpaaka na-egosi na ịgbalite ahụ nwere ike jikọta ya na nkwụsị nke nri ndị neurons na-achịkwa na akụkụ parabrachial nucleus, si otú ahụ na-achịkwa ọkwa glucose ọbara ^[4]..

Iwu Gastrointestinal: Semaglutid na-arụ ọrụ na ndị na-anabata GLP-1 na eriri afọ. Site n'ụzọ afferent nke akwara vagus, ọ na-eme n'akụkụ ụbụrụ dị ka nucleus nke traktị naanị ya na dorsal moto nucleus nke akwara vagus iji dozie motility eriri afọ. Ọ nwere ike igbochi mkpụkọ nke antrum gastric, welie esemokwu nke sphincter pyloric, ịgbatị oge obibi nri n'ime afọ, na-egbu oge ịbanye na duodenum, na-egbochi ịrị elu ngwa ngwa nke glucose ọbara postprandial na ime ka glucose ọbara gbanwee ka ọ kwụsie ike ^[5] (Katsurada K, 2016). Tụkwasị na nke ahụ, Semaglutid na-arụ ọrụ na GLP-1 ndị na-anabata ya na usoro nhụjuanya nke etiti, karịsịa na mpaghara ndị dị ka arcuate nucleus na paraventricular nucleus nke hypothalamus. Ọ na-egbochi mwepụta nke ihe na-akpali agụụ mmekọahụ dị ka neuropeptide Y (NPY) na protein metụtara agouti (AgRP), ma n'otu oge ahụ na-arụ ọrụ pro-opiomelanocortin (POMC) neurons, na-akwalite nzuzo nke α-melanocyte-akpali akpali hormone (α-MSH) ^[5] . Mmetụta ndị a na-emepụta mmetụta nke satiety, belata agụụ, na ibelata oriri nri, na-enwe mmetụta dị mma na njikwa glucose ọbara n'ụzọ na-apụtaghị ìhè.

Nchedo obi obi: Semaglutid nwere ike ịkwalite mkpụrụ ndụ endothelial vaskụla iji hapụ ihe ndị na-akpata vasodilatory dị ka nitric oxide (NO), na-eme ka ikike dilation vaskụla na-eme ka ọbara gbasaa. N'otu oge ahụ, ọ na-egbochi nzaghachi mkpali na nrụgide oxidative, na-ebelata mmebi nke sel endothelial vaskụla, ma na-ebelata ohere nke atherosclerosis. Ọzọkwa, site n'ibelata agụụ na iri nri, Semaglutid na-enyere aka na mbelata ibu, na-emezi nsogbu metabolism lipid, na-ebelata ọkwa nke triglycerides na obere njupụta lipoprotein cholesterol (LDL-C), ma na-abawanye ọkwa nke lipoprotein cholesterol dị elu (HDL-C). Ọ nwekwara ike inwe mmetụta bara uru na ọbara mgbali elu site n'ịhazi hemodynamics renal na ọrụ neuroendocrine, na-ebelata ihe ize ndụ nke ọbara mgbali elu na ọrịa obi na ọrịa obi ^[6]..

Semaglutid na usoro ntụgharị nke WAT na ntụgharị BAT na ịgbalite BAT.

Isi mmalite: PubMed ^[12]

Gịnị bụ isi nnwale na ọmụmụ?

Nhazi na njikarịcha nhazi kemịkalụ: Mgbe ị na-emepụta Semaglutid, a nakweere usoro ngbanwe nke njikọta na albumin iji gbasaa ogologo oge nke ọgwụ ahụ. Site n'ịchọpụta njikọ kachasị mma nke fatty acids na njikọ njikọ, ka ị na-ejigide nrụpụta nke GLP-1 receptor (GLP-1R), a na-abawanye ikike ijikọ na albumin ^[7]..

Ngwa ọgwụ: Semaglutid bụ glucagon-dị ka peptide-1 agonist receptor (GLP-1 RA) nke nwere ogologo oge mkpochapụ ọkara ndụ, na-enye ohere maka injection subcutaneous otu ugboro kwa izu. N'ime ndị ọrịa nwere ụdị 2 metabolism (T2DM), mmetụta mbelata arọ nke injection subcutaneous nke Semaglutid otu ugboro kwa izu dị elu karịa nke GLP-1RA ndị ọzọ otu ugboro kwa izu. N'ime usoro nyocha nke usoro nke II maka ndị ọrịa buru ibu na-enweghị T2DM, injection subcutaneous nke Semaglutid otu ugboro kwa ụbọchị gosipụtara mmetụta mbelata dị mma karịa placebo na otu ugboro kwa ụbọchị 3.0 mg liraglutide. Ogo ọnwụ nke Semaglutid kpatara n'ọmụmụ ihe a karịrị ụkpụrụ maka ọgwụ na-ebelata ibu nke European Medicines Agency (EMA) na US Food and Drug Administration (FDA) setịpụrụ, na ọ dịghị mma, na-egosi na otu ugboro n'ime subcutaneous injection nke Semaglutid nwere ike ịghọ ọgwụ na-ebelata ibu n'ọdịnihu ^[8].

Ọgwụgwọ ọrịa obi na-arịa ọrịa obi site na imeziwanye ọrụ obi: Nsonaazụ nke STEP-HFpEF ule gosiri na nnukwu ọgwụ antidiabetic glucagon-like peptide 1 agonist Semaglutid mere ka ihe mgbaàmà ndị metụtara nkụda obi na-eme ka ọ dịkwuo mma site n'ichekwa ejection fraction (HFpEF) ma belata ọkwa nke N-terminal natype-NTP-BN. Nnwale nyocha achọpụtala na ọgwụgwọ siri ike na Semaglutid nwere ike ịbawanye esemokwu nke trabeculae mmadụ karịa ugboro atọ n'ụzọ dabere na dose, na-enweghị mmụba nke arrhythmia. Mmetụta a nwere ike ịbụ n'ihi mmụba nke Ca2+ site na reticulum sarcoplasmic. Ọgwụgwọ Semaglutid dị elu na ndị ọrịa nwere nkụda mmụọ nwere ike imeziwanye ọrụ atrial, si otú ahụ na-ebelata mgbaàmà ^[9].

A na-enyocha Semaglutid maka ọgwụgwọ steatohepatitis na-adịghị egbu egbu (NASH): Nhazi ezi uche nke Semaglutid enyela nnukwu onyinye iji meziwanye njikwa glucose ọbara, ịdị arọ ahụ, ọbara mgbali elu, lipids ọbara, ọrụ β-cell, na usoro obi na ndị ọrịa nwere ụdị 2 metabolism. Tụkwasị na nke ahụ, mmepe nke usoro ọnụ nke Semaglutid nwere ike inye uru ọzọ n'ihe gbasara nnabata ọgwụgwọ ndị ọrịa ^[7].

Kedu ihe dị iche na mmetụta mbelata nke Semaglutid n'etiti ndị mmadụ dị iche iche?

Ndị okenye nwere ọrịa obi na-adịbu adị, oke ibu ma ọ bụ oke ibu ma na-enweghị metabolism: N'ime SELECT cardiovascular results trial, Semaglutid belatara ihe omume obi ọjọọ dị njọ site na 20% na ndị okenye 17,604 nwere ọrịa obi dị adị, oke ibu ma ọ bụ oke ibu, na enweghị metabolism ^[10] (Ryan DH, 2024). Na nyocha a akọwapụtara nke ọma, ndị nchọpụta nyochara mmetụta Semaglutid na ịdị arọ ahụ, nsonaazụ anthropometric, nchekwa, na nnabata dị ka isi ihe nrịbama ahụ (BMI) si dị. Ndị ọrịa na-anata Semaglutid nwetara mbelata ahụ na-aga n'ihu n'ime izu 65, na-adịgide ruo afọ 4. N'ime izu 208, ma e jiri ya tụnyere ndị otu placebo, Semaglutid mere ka ọnụ ọgụgụ ahụ dị elu (-10.2%), okirikiri ukwu (-7.7 cm), na n'úkwù na ịdị elu (-6.9%), ebe ndị otu placebo nwere mbelata nke (-1.5%, -1.3 cm, na -1.0%) n'otu n'otu, na ebebo niile dị ịrịba ama. Mbelata ibu arọ nke ụlọ ọgwụ mere na ma ndị nwoke ma ndị nwanyị, agbụrụ niile, ụdị ahụ, na mpaghara. Ejikọtara Semaglutid na obere ihe ọjọọ dị njọ. Maka ụdị BMI nke ọ bụla (<30, 30 na <35, 35 ka <40, na ≥40 kg / m²), ihe omume dị njọ nke Semaglutid (ọnụọgụ nke ihe omume a na-ahụ kwa afọ 100 mmadụ) dị ala (43.23, 43.54, 51.07, 6, 4, 51.07, na Semaglutid, na 43.54, 51.07, 6, 4, 51, 5, 4, na 51.00, na 43.54, 51.00, 4,8, na Semaglutid, na 43.54, 51.00. 49.66, 52.73, na 60.85 maka placebo). Ejikọtara Semaglutid na mmụba nke nkwụsị nke ngwaahịa nnwale ahụ. Ka ngalaba BMI na-ebelata, ọnụego nkwụsị ahụ mụbara. N'ime ule SELECT, na izu 208, Semaglutid rụpụtara nnukwu ibu dị arọ nke ụlọ ọgwụ na mmụba na ụkpụrụ anthropometric ma e jiri ya tụnyere placebo, na ọnwụ dị arọ nọgidere ruo afọ 4.

Ndị mmadụ n'otu n'otu dị oke ibu ma ọ bụ buru oke ibu ma na-enweghị metabolism: Nyocha nyocha nyocha nke ọma na nchekwa nke Semaglutid na ndị nwere oke ibu ma ọ bụ buru ibu ma na-enweghị metabolism ^[11] . Nyochaa a chịkọtara nsonaazụ nke ọtụtụ nnwale ụlọ ọgwụ, na-ekwusi ike mmetụta Semaglutid na oke ibu, paramita metabolic, na nsonaazụ ahụike zuru oke. Nsonaazụ gosiri na Semaglutid jikọtara ya na oke ibu dị arọ na mmụba na ihe ngosi ahụike metụtara oke ibu, yana ọ nwere ike ịbụ nhọrọ ọgwụgwọ bara uru maka ndị ọrịa buru ibu.

Ndị ọrịa na-abụghị ndị ọrịa mamịrị (ihe akaebe sitere na ọtụtụ RCTs): N'ime ule 4 a na-achịkwa nke a na-achịkwaghị achịkwa, ndị ọrịa nwere ịdị arọ nke 96 ruo 105 n'arọ natara ntụtụ subcutaneous kwa izu nke 2.4 mg nke Semaglutid na ndụ ndụ (ndụmọdụ, nri, na mmega ahụ) maka ọgwụgwọ ọnwụ. Otu ule a na-achịkwa nke a na-achịkwa maka ndị ọrịa na-abụghị ndị ọrịa mamịrị (N = 1961) gosiri na mgbe izu 68 gasịrị, nkezi ibu arọ bụ 15% (15 n'arọ), bụ nke dị nnọọ iche na 2% (3 n'arọ) na placebo otu. Ọnụ ọgụgụ nke ndị ọrịa nwere oke ibu nke ≥5% bụ 86% ma e jiri ya tụnyere 32% na otu placebo, na ọnụ ọgụgụ dị mkpa iji gwọọ (NNT) = 2; Ọnụ ọgụgụ nke ndị ọrịa nwere oke ibu nke ≥10% bụ 69% ma e jiri ya tụnyere 12% na placebo otu, na NNT = 2. Mbelata ịdị arọ na-agbada n'ihe dị ka izu 60. Ọnụ ọgụgụ nke ihe ndị na-adịghị mma nke eriri afọ (AEs) bụ 74% ma e jiri ya tụnyere 48% na placebo, na ọnụ ọgụgụ dị mkpa iji merụọ (NNH) = 3. Ọnụ ọgụgụ nke ndị ọrịa na-akwụsị ọgwụgwọ n'ihi ihe ọjọọ bụ 7% ma e jiri ya tụnyere 3% na placebo otu, na NNH = 25. N'ihe ọzọ a na-achịkwaghị achịkwa na-achịkwa ndụ 1 n'ime ndụ ndụ 1 N'ime usoro ndụ 1), N'ime usoro ndụ 1 na-enweghị atụ nke na-adịghị agwụ agwụ (N) Otu Semaglutid bụ 16% (17 n'arọ), nke dị iche na 6% (6 n'arọ) na otu placebo. N'ime nyocha nyocha nke usoro nyocha maka ndị ọrịa nwere ọrịa shuga (N = 1210), a na-enye ndị ọrịa 2.4 mg n

N'ikpeazụ, Semaglutid bụ GLP-1 agonist agonist nke nwere uru ngwa n'ọtụtụ mpaghara. N'ihe gbasara ọgwụgwọ metabolism, ọ na-achịkwa ọkwa glucose ọbara nke ọma site na ijikọ ndị na-anabata GLP-1, na-akwalite mmepụta insulin, na igbochi mwepụta glucagon, na-enye nhọrọ ọgwụgwọ dị mkpa maka ndị ọrịa nwere ụdị ọrịa shuga 2. N'akụkụ nke ọgwụgwọ oke ibu, Semaglutid na-ebelata ike oriri site na usoro ndị dị ka nkwụsị nke agụụ etiti na igbu oge na-egbu oge, na-enyere ndị ọrịa buru ibu aka ịkwụsị ibu ma melite ọnọdụ ha. Na mgbakwunye, Semaglutid na-egosikwa atụmanya ngwa nwere ike na mgbochi na ọgwụgwọ ọrịa obi. Ọganihu ya nke ihe ize ndụ nke obi na-enye ụzọ ọhụrụ iji belata ihe omume nke obi.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Hegner P bụ onye nyocha na Mahadum Regensburg. Ọrụ ya gụnyere Chemistry, Cardiovascular System, na Cardiology. Na Chemistry, ọ na-enyocha mmeghachi omume jikọtara na ahụike obi. N'ime usoro ọmụmụ Cardiovascular, ọ na-enyocha obi na ọrụ arịa, na-achọ nghọta ọgwụgwọ. Nnyocha nke Cardiology ya na-elekwasị anya na mgbochi ọrịa obi, nchọpụta, na ọgwụgwọ.

Enyemaka Hegner dị oke mkpa. Nghọta kemịkalụ ya akwalitela mmepe ọgwụ obi ọhụrụ. Ọrụ ya na usoro obi na arịa emewo ka nghọta nke ọrịa obi. Na ụlọ ọgwụ, nchọpụta ya emeela ka nlekọta ọrịa obi dịkwuo mma, na-ebuli ụkpụrụ nlekọta ndị ọrịa. N'ozuzu, ụzọ dị iche iche nke Hegner na-eme ka nkà mmụta ọgwụ na-eme ka obi dịkwuo mma, na-enye olileanya maka mbelata ibu ọrịa yana nsonaazụ ndị ọrịa ka mma. Edepụtara Hegner P na ntụaka nke ntụaka ^[9].

▎ Okwu ndị dị mkpa

[1] Memon A, Tehrim M, Kumari B. Semaglutid: chi ọbụbọ ọhụrụ maka ndị ọrịa mamịrị[J]. Akwụkwọ akụkọ nke Pakistan Medical Association, 2023,73 (3): 721.DOI: 10.47391 / JPMA.7558.

[2] Ma H, Huang W, Wang X, et al. Nghọta ihe arụrụ arụ na ịgbalite GLP-1R site na obere agonist molecule[J]. Nnyocha cell, 2020,30 (12): 1140-1142.DOI:10.1038/s41422-020-0384-8.

[3] Kim HS, Jung C H. Oral Semaglutid, Glucagon nke mbụ ingestible-dị ka Peptide-1 Onye na-anabata Agonist: Ọ nwere ike ịbụ Mgbo Ime Anwansi maka Ụdị 2 Metabolism?[J]. Akwụkwọ akụkọ International nke Science Molecular, 2021,22(18).DOI:10.3390/ijms22189936.

[4] Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutid na-ebelata ibu ahụ n'ime òké site na ụzọ neural na-ekesa [J]. Jci Insight, 2020,5 (6).DOI:10.1172/jci.insight.133429.

[5] Katsurada K, Yada T. Mmetụta akwara nke gut- na ụbụrụ sitere na glucagon-dị ka peptide-1 na agonist onye na-anabata ya [J]. Akwụkwọ akụkọ Metabolism Investigation, 2016,7: 64-69.DOI: 10.1111 / jdi.12464.

[6] Ryan DH, Lingvay I, Colhoun HM, et al. Mmetụta Semaglutid na nsonaazụ Cardiovascular na ndị nwere oke ibu ma ọ bụ oke ibu (SELECT) echiche na imewe [J]. Akwụkwọ akụkọ obi America, 2020,229:61-69.DOI:10.1016/j.ahj.2020.07.008.

[7] Knudsen LB, Lau J. Nchọpụta na mmepe nke Liraglutide na Semaglutid[J]. Ihu ihu na Endocrinology, 2019,10.DOI:10.3389/fendo.2019.00155.

[8] Christou GA, Katiki N, Blundell J, et al. Semaglutid dị ka ọgwụ mgbochi oke ibu na-ekwe nkwa [J]. Nlebanya oke ibu, 2019,20(6):805-815.DOI:10.1111/obr.12839.

[9] Hegner P, Seitz S, Schopka S, et al. Semaglutid na-akwalite ọrụ nkwekọrịta na atrium mmadụ dịpụrụ adịpụ[J]. Akwụkwọ akụkọ obi European, 2024,45.DOI:10.1093/eurheartj/ehae666.3729.

[10] Ryan DH, Lingvay I, Deanfield J, et al. Mmetụta ọnwụ ogologo oge nke semaglutide na oke ibu na-enweghị metabolism na nnwale SELECT[J]. Ọgwụ okike, 2024,30 (7): 2049-2057.DOI: 10.1038/s41591-024-02996-7.

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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) akwadobeghị 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.