Cagrilintide 10 mg

▎ Cagrilintide Structure

▎ Kev Tshawb Fawb Cagrilintide

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm Cagrilintide?

Cagrilintide yog dual amylin thiab calcitonin receptor agonist (DACRA) tsim los ntawm cov qauv ntawm amylin. Amylin yog zais los ntawm pancreatic islet β hlwb thiab ua haujlwm hauv kev hais kwv txhiaj nrog insulin kom ua haujlwm ntau lub cev. Nws tuaj yeem ua rau muaj kev xav ntawm satiety thiab txo cov khoom noj kom tsawg, feem ntau los ntawm kev ua kom cov receptors hauv thaj chaw postrema ntawm lub hauv paus ntawm plaub ventricle. Cov teeb liab neural raug xa mus rau lub forebrain los ntawm lub hauv paus ntawm lub solitary ib ntsuj av thiab kuj yuav kis tau mus rau lub lateral hypothalamic cheeb tsam thiab lwm pab pawg neeg nuclear ntawm lub lateral parabrachial nucleus, yog li ntawd txaus siab rau qhov chaw satiety thiab inhibiting zaub mov noj ^[1] . Amylin tuaj yeem tswj hwm cov piam thaj hauv tsev los ntawm inhibiting qhov tso tawm ntawm insulin thiab glucagon kom tswj cov ntshav qabzib hauv cov ntshav ^[2] . Nws cov txheej txheem suav nrog kev cuam tshuam ncaj qha rau ntawm pancreatic islet α hlwb thiab kev tswj tsis ncaj ntawm glucagon secretion los ntawm neural signals hauv hypothalamus. Hauv cov neeg mob ntshav qab zib mellitus, kev puas tsuaj ntawm β hlwb ua rau txo qis hauv amylin secretion. Amylin koom nrog kev tswj hwm cov piam thaj homeostasis los ntawm inhibiting gastric emptying thiab postprandial hepatic qabzib ntau lawm, txo cov ntshav qabzib hloov pauv hauv postprandial. Nws tseem tuaj yeem ncua kev ua pa ntawm plab, inhibit plab hnyuv peristalsis, ncua lub sijhawm nyob ntawm zaub mov, thiab tiv thaiv kom tsis txhob muaj ntshav qabzib nce ntxiv. Txawm li cas los xij, luv luv ib nrab-lub neej ntawm ntuj amylin txwv nws daim ntawv thov kev kho mob. Txawm hais tias pramlintide muaj nyob rau hauv cov tshuaj adjuvant, nws yuav tsum tau txhaj peb zaug ib hnub, uas yog qhov tsis yooj yim thiab ua rau tsis ua raws cai ^[3] . Txhawm rau daws qhov teeb meem no, Cagrilintide tau tsim. Nws txoj kev tshawb fawb thiab kev loj hlob yog ua raws li kev nkag siab tob txog lub cev kev ua haujlwm ntawm ntuj amylin, tsom mus rau kev ua raws li nws cov txheej txheem ntawm kev ua haujlwm thaum txhim kho kev ruaj ntseg thiab kev ua haujlwm ntev ntawm cov tshuaj kom tau raws li kev xav tau ntawm kev kho mob.

Cagrilintide yog dab tsi?

Cagrilintide yog ib qho tshiab ntev-ua yeeb yam amylin analog nrog lub peev xwm zoo, tau pom thawj zaug ua tau zoo hauv kev kho mob rog thiab ntshav qab zib. Nws tau raug lipidated thiab muaj cov yam ntxwv ruaj khov thiab ua haujlwm ntev ^[3] . Amylin raug tso tawm nrog insulin los ntawm pancreatic β hlwb thiab ua rau muaj kev xav ntawm satiety los ntawm kev ua haujlwm ntawm thaj chaw homeostatic thiab txaus siab ntawm lub hlwb. Raws li ib qho analogue, Cagrilintide tuaj yeem ua raws li cov txiaj ntsig no, ua rau muaj kev txaus siab los pab tswj lub cev hnyav. Nyob rau tib lub sijhawm, raws li ib tug dual amylin thiab calcitonin receptor agonist (DACRA), nws yog muab los ntawm amylin qaum thiab muaj ib tug tshwj xeeb mechanism nyob rau hauv metabolic kev cai.

Qauv qauv ntawm Cagrinlintide

Source: PubMed ^[3]

Dab tsi yog cov kev siv cuam tshuam ntawm Cagrilintide?

Hauv kev sim tshuaj, Cagrilintide tau ua tiav cov txiaj ntsig zoo hauv kev ua kom poob phaus. Piv txwv li, nyob rau hauv ib tug multicenter, randomized, ob-dig muag, placebo-tswj, thiab active comparator Phase 2 koob tshuaj-nrhiav mus sib hais, piv nrog cov placebo pab pawg neeg, qhov nruab nrab feem pua ​​​​ntawm qhov hnyav poob los ntawm lub hauv paus hauv txhua pawg koob tshuaj Cagrilintide (0.3 - 4.5 mg) (6.0% - 10.8%) qhov chaw siab dua (3.8%). Qhov poob phaus hauv pawg 4.5 mg kuj tseem ntau dua li ntawm liraglutide 3.0 mg pawg (10.8% vs. 9.0%), qhia tias nws tuaj yeem yog qhov kev xaiv zoo rau kev tswj qhov hnyav ^[4] . Cagrilintide muaj qhov sib txawv tab sis cuam tshuam txog kev ua haujlwm piv nrog GLP-1 receptor agonist semaglutide. Semaglutid txo qis qab los noj mov, nce insulin secretion, thiab ncua lub plab zom mov los ntawm kev ua ntawm GLP-1 receptors hauv hypothalamus, thaum Cagrilintide txo qis qab los ntawm kev ua kom cov amylin receptors. Kev siv ua ke ntawm ob tuaj yeem tsim cov nyhuv superimposed, txhim kho qhov hnyav poob ^[5] . Muab qhov nyuaj ntawm kev rog rog, qhov kev kho mob ua ke no yog qhov tsim nyog thiab muaj txiaj ntsig zoo.

Hauv cov neeg mob uas muaj ntshav qab zib hom 2, Cagrilintide kuj tau pom tias muaj peev xwm tswj cov ntshav qabzib zoo. Cov kev tshawb fawb soj ntsuam tau pom tias nws muaj kev ruaj ntseg zoo thiab muaj txiaj ntsig zoo hauv kev kho mob rog rog thiab ntshav qab zib hom 2. Piv txwv li, hauv kev sim tshuaj ntsuam xyuas ntawm cov neeg mob ntshav qab zib hom 2, kev sib xyaw ua ke ntawm Cagrilintide thiab GLP-1 receptor agonist semaglutide tau pom zoo tswj cov ntshav qabzib thiab txo qhov hnyav ^[6] . Lwm qhov kev sim kuj qhia tau tias nws muaj peev xwm ua tau zoo thiab muaj kev nyab xeeb thaum siv ib leeg lossis ua ke nrog semaglutide ^[6] , vim tias kev ruaj ntseg ntawm cov tshuaj muaj feem cuam tshuam nrog nws txoj kev kam rau siab thiab kev nyab xeeb.

Tsis tas li ntawd, Cagrilintide tau txais txiaj ntsig zoo hauv kev sim tshuaj. Hauv Phase 2-nrhiav koob tshuaj, qhov kev txiav tawm mus tas li hauv txhua pab pawg kho mob tau zoo sib xws, feem ntau yog vim muaj cov xwm txheej tsis zoo. Txawm li cas los xij, cov xwm txheej tshwm sim feem ntau yog mob plab hnyuv thiab qhov chaw txhaj tshuaj, thiab feem ntau ntawm lawv yog me me mus rau nruab nrab. Nyob rau hauv ib qho randomized, tswj Phase 1b mus sib hais, kev kho mob ua ke ntawm Cagrilintide thiab 2.4 mg semaglutide kuj pom zoo rau kev zam thiab kev nyab xeeb ^[7] . Cov kev sim loj dua thiab ntev ntev yuav tsum tau muaj nyob rau yav tom ntej txhawm rau ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm kev kho ua ke no.

Cagrilintide coj kev cia siab tshiab rau kev kho mob rog rog thiab ntshav qab zib hom 2. Nws muab kev kho mob tshiab rau cov neeg mob rog, tshwj xeeb tshaj yog cov neeg uas tsis teb zoo rau kev ua neej nyob thiab tsis haum rau kev phais bariatric. Nws cov txheej txheem tshwj xeeb ntawm kev ua tau muab cov tswv yim tshiab thiab cov hau kev rau kev kho mob rog, thiab nws yuav muaj txiaj ntsig ntau dua li cov tshuaj poob phaus (D'Ascanio AM, 2024). Cov ntaub ntawv ua tiav ntawm kev siv ua ke ntawm Cagrilintide thiab semaglutide (CagriSema) qhia tau hais tias kev kho ntau lub hom phiaj ua ke yog lub tswv yim zoo los txhim kho cov lus teb rau kev rog rog ^[6] . Cov qauv no muab lub ntsiab lus tshiab rau kev tswj hwm kev rog thiab tseem ua rau muaj kev txhim kho metabolic tseem ceeb rau cov neeg mob ntshav qab zib hom 2.

Hauv kev xaus, raws li kev ua yeeb yam ntev ntev amylin analog, Cagrilintide muaj peev xwm tseem ceeb rau kev poob phaus thiab tswj ntshav qabzib. Nws activates lub satiety signaling txoj kev los ntawm mimicking qhov kev txiav txim ntawm amylin thiab tswj cov metabolism hauv ib tug dual receptor agonist. Kev sim tshuaj ntsuam xyuas tau pom tias Cagrilintide, ib leeg lossis ua ke nrog semaglutide, tuaj yeem txo lub cev hnyav thiab ua kom zoo. Tsis tas li ntawd, nws kuj tau qhia txog kev tswj cov ntshav qabzib zoo hauv cov neeg mob uas muaj ntshav qab zib hom 2, muab kev kho mob tshiab rau kev kho mob rog thiab ntshav qab zib, ua kom muaj qhov sib txawv ntawm cov kev kho mob uas twb muaj lawm, tshwj xeeb tshaj yog rau cov neeg mob uas tsis teb zoo rau kev ua neej nyob thiab tsis haum rau kev phais. Nws txoj kev kho ntau lub hom phiaj muab tswv yim tshiab rau kev tswj cov kab mob metabolic.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Dr. DCW Lau yog ib tug xibfwb ntawm Cumming School of Medicine, University of Calgary, Canada. Nws cov kev tshawb fawb txog kev noj qab haus huv suav nrog endocrinology thiab metabolism, kev siv tshuaj dav dav thiab sab hauv, kab mob plawv thiab mob plawv, kev noj qab haus huv pej xeem, kev noj qab haus huv thiab kev ua haujlwm, nrog rau oncology. Nws tseem tuav txoj haujlwm nrog Alberta Health Services (AHS) thiab Obesity Canada thiab ua haujlwm ntawm Julia McFarlane Diabetes Research Center. Dr. Lau muaj kev paub dhau los hauv kev tshawb fawb txog ntshav qab zib thiab rog rog, nrog rau nws txoj haujlwm tau luam tawm hauv cov ntawv xov xwm kev kawm xws li Canadian Journal of Diabetes. Dr. DCW tau teev nyob rau hauv cov ntaub ntawv siv los ntawm kev hais tawm [4].

▎ Cov Lus Qhia Tseem Ceeb

[1] Hansen KE, Murali S, Chaves IZ, et al. Glycomacropeptide cuam tshuam rau Amylin-Mediated Satiety, Postprandial Markers ntawm Glucose Homeostasis, thiab Fecal Microbiome nyob rau hauv Obese Postmenopausal Women [J]. Phau ntawv Journal of Nutrition, 2023,153(7):1915-1929.DOI:10.1016/j.tjnut.2023.03.014.

[2] Ling W, Huang Y, Qiao Y, et al. Tib neeg Amylin: Los ntawm Pathology rau Physiology thiab Pharmacology [J]. Tam sim no Protein & Peptide Science, 2019,20(9): 944-957.DOI: 10.2174/ 13892037206 66 19032811183 3.

[3] Kruse T, Hansen JL, Dahl K, et al. Kev loj hlob ntawm Cagrilintide, Kev Ua Haujlwm Ntev Amylin Analogue [J]. Phau ntawv Journal of Medicinal Chemistry, 2021,64(15):11183-11194.DOI:10.1021/acs.jmedchem.1c00565.

[4] Lau DCW, Erichsen L, Francisco AM, et al. Ib lub limtiam cagrilintide rau kev tswj qhov hnyav hauv cov neeg uas rog dhau thiab rog: ntau qhov chaw, randomised, ob-dig muag, cov tshuaj placebo-tswj thiab active-tswj, koob tshuaj-nrhiav theem 2 mus sib [J]. Lancet, 2021,398(10317):2160-2172.DOI:10.1016/S0140-6736(21)01751-7.

[5] D'Ascanio AM, Mullally JA, Frishman W H. Cagrilintide: Ntev-Amylin Analog rau Kev Kho Mob Rog [J]. Cardiology in Review, 2024,32(1):83-90.DOI:10.1097/CRD.0000000000000513.

[6] Frias JP, Deenadayalan S, Erichsen L, et al. Kev ua tau zoo thiab kev nyab xeeb ntawm kev sib koom ua ke ib zaug ib lub lis piam cagrilintide 2.4 mg nrog ib zaug ib lub lim tiam semaglutide 2.4 mg hauv hom 2 mob ntshav qab zib: multicentre, randomised, ob-dig muag, active-tswj, theem 2 sim [J]. Lancet, 2023,402(10403):720-730.DOI:10.1016/S0140-6736(23)01163-7.

[7] Enebo LB, Berthelsen KK, Kankam M, et al. Kev nyab xeeb, tolerability, pharmacokinetics, thiab pharmacodynamics ntawm concomitant kev tswj hwm ntawm ntau koob tshuaj cagrilintide nrog semaglutide 2.4 mg rau kev tswj qhov hnyav: randomised, tswj, theem 1b sim [J]. Lancet, 2021,397(10286):1736-1748.DOI:10.1016/S0140-6736(21)00845-X.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.