Cagrilintide 5 mg

▎ Cagrilintide Structure

▎ Kev Tshawb Fawb Cagrilintide

Lub hauv paus chiv keeb ntawm Cagrilintide yog dab tsi?

Cagrilintide - ib qho analogue ntawm amylin:

Amylin yog ib yam tshuaj uas tso tawm los ntawm pancreatic islet beta hlwb. Nyob rau hauv cov xwm txheej ntawm lub cev, nws koom tes nrog insulin thiab muaj ntau yam haujlwm tseem ceeb ntawm lub cev.

Ua ntej, amylin plays lub luag haujlwm tseem ceeb hauv kev ua kom satiety thiab txo cov khoom noj. Nws cov txheej txheem ntawm kev nqis tes ua feem ntau cuam tshuam nrog kev ua kom cov receptors hauv Cheeb Tsam Postrema ntawm lub hauv paus ntawm plaub ventricle. Cov teeb liab neural raug xa mus rau lub forebrain ntawm lub Nucleus ntawm lub Solitary Tract. Tib lub sijhawm, lawv tuaj yeem raug xa mus rau Lateral Hypothalamic Area thiab lwm pawg hypothalamic nuclear los ntawm Lateral Parabrachial Nucleus. Amylin muaj lub peev xwm los txhawb qhov chaw satiety ntawm lub cev thiab inhibit kev noj zaub mov hauv cov tsiaj ^[1].

Amylin muaj peev xwm tswj hwm cov piam thaj hauv homeostasis, uas ua tiav los ntawm inhibiting qhov tso tawm ntawm insulin thiab glucagon ^[2] . Qhov kev ua haujlwm no ua rau muaj txiaj ntsig zoo rau kev tswj hwm kev ruaj ntseg ntawm cov ntshav qabzib thiab tuav qhov tseem ceeb rau kev kho mob xws li ntshav qab zib.

Ntxiv mus, amylin exerts nws cov teebmeem los ntawm influencing tso tawm ntawm neurotransmitters. Piv txwv li, nws inhibits qhov tso tawm ntawm dopamine nyob rau hauv hypothalamus ntawm nas, thaum muaj kev cuam tshuam me me rau norepinephrine thiab serotonin ^[3] . Hauv cov ntsiab lus ntawm cov piam thaj homeostasis, amylin tswj cov ntshav qabzib ruaj khov los ntawm kev txo qis ntawm cov tshuaj insulin thiab glucagon. Nws cov txheej txheem suav nrog ncaj qha ua haujlwm ntawm pancreatic islet α hlwb thiab tsis ncaj qha tswj glucagon secretion los ntawm neural signal transduction hauv hypothalamus. Hauv cov neeg mob ntshav qab zib mellitus, kev puas tsuaj ntawm β hlwb tsis yog tsuas yog ua rau insulin tsis txaus, tab sis kuj ua rau txo qis hauv kev tso tawm ntawm C-peptide thiab amylin. Amylin pom tau tias koom nrog hauv kev tswj hwm cov piam thaj hauv tsev los ntawm inhibiting gastric emptying thiab postprandial hepatic qabzib ntau lawm, thaum kawg txo cov ntshav qabzib hloov pauv ^[4] . Tsis tas li ntawd, amylin tuaj yeem ncua lub plab zom mov, inhibit plab hnyuv peristalsis los ntawm lub hauv nruab nrab lub paj hlwb, thiab ua kom lub sijhawm nyob ntawm cov zaub mov hauv txoj hnyuv, yog li tiv thaiv kev nce ntshav qabzib sai.

Txawm li cas los xij, amylin muaj qhov luv luv ib nrab-lub neej, uas txwv tsis pub nws daim ntawv thov kho mob. Kev tshawb fawb qhia tias tam sim no amylin analog, pramlintide, ua ib qho tshuaj ntxiv rau kev kho mob ntshav qab zib, yuav tsum tau tswj hwm peb zaug ib hnub. Qhov no tsis tsuas yog ua rau tsis yooj yim rau cov neeg mob tab sis kuj txo lawv txoj kev ua raws li ^[5] . Txhawm rau daws qhov teeb meem ntawm luv luv ib nrab-lub neej ntawm ntuj amylin, Cagrilintide tau raug tsim los ua ib qho analog ua haujlwm ntev. Txoj kev loj hlob ntawm Cagrilintide yog nyob rau hauv kev nkag siab tob txog lub physiological functions ntawm ntuj amylin. Nws lub hom phiaj los simulate cov txheej txheem ntawm kev txiav txim ntawm amylin thaum txhim kho kev ruaj ntseg thiab ua haujlwm ntev ntawm cov tshuaj kom tau raws li cov kev cai ntawm kev kho mob.

Lub peev xwm thiab Pharmacological Properties ntawm Cagrilintide

Cagrilintide yog ib qho tshiab ntev-ua yeeb yam amylin analogue nrog lub peev xwm tseem ceeb, ua kom pom cov txiaj ntsig zoo tshaj plaws hauv kev kho mob rog thiab ntshav qab zib. Nws yog lipidated thiab muaj cov yam ntxwv ua haujlwm ntev ntev ^[5] . Amylin yog cov tshuaj hormones tso tawm los ntawm pancreatic β hlwb nrog rau cov tshuaj insulin, uas ua rau muaj kev txaus siab los ntawm kev ua haujlwm ntawm thaj chaw homeostatic thiab hedonic ntawm lub hlwb. Raws li ib qho analogue ntawm amylin, Cagrilintide tuaj yeem ua raws li cov txiaj ntsig no, ua rau muaj kev txaus siab thiab yog li pab tswj qhov hnyav. Ntxiv mus, Cagrilintide yog ib tug dual amylin thiab calcitonin receptor agonist, muab los ntawm amylin qaum, endowing nws nrog ib tug tshwj xeeb mechanism ntawm kev txiav txim nyob rau hauv metabolic kev cai.

Kev Txhim Kho ntawm Kev Tshawb Fawb Kev Tshawb Fawb ntawm Cagrilintide

Hauv kev sim tshuaj, Cagrilintide tau txais 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-tswj theem 2 koob tshuaj-nrhiav mus sib hais, cov neeg koom nrog kho nrog Cagrilintide pom tau hais tias yuag poob ntau dua piv rau cov neeg tau txais cov placebo. Qhov feem pua ​​​​ntawm qhov hnyav txo los ntawm cov hauv paus hauv paus rau tag nrho cov koob tshuaj Cagrilintide (0.3 - 4.5 mg) yog siab dua (6.0% - 10.8%) dua li ntawm pawg placebo (3.0%). Qhov kev txo qis hauv cov pab pawg kho nrog 4.5 mg ntawm Cagrilintide kuj tseem ntau dua li cov pab pawg kho nrog 3.0 mg ntawm liraglutide (10.8% vs. 9.0%). Cov txiaj ntsig no qhia tias Cagrilintide tuaj yeem yog qhov kev xaiv zoo rau kev tswj hwm qhov hnyav ^[6].

Cagrilintide thiab GLP-1 receptor agonist semaglutide muaj qhov sib txawv tseem cuam tshuam txog kev ua haujlwm. Semaglutid siv nws cov teebmeem los ntawm kev ua haujlwm ntawm GLP-1 receptors hauv hypothalamus, uas ua rau txo qis hauv qab los noj mov, nce hauv insulin secretion, thiab qeeb hauv plab hnyuv. Conversely, Cagrilintide ntxiv suppresses qab los noj mov los ntawm activating amylin receptors. Kev tswj hwm kev sib koom ua ke ntawm ob tus neeg ua haujlwm no ua rau muaj txiaj ntsig zoo rau kev noj qab haus huv los ntawm ntau lub tswv yim, ua kom muaj txiaj ntsig zoo ntawm qhov hnyav ^[7] . Muab qhov zoo sib xws ntawm kev rog rog, kev kho mob sib xyaw ua ke tsom mus rau ntau yam pathophysiological endpoints sawv cev rau lub tswv yim muaj txiaj ntsig thiab muaj txiaj ntsig.

Tsis tas li ntawd, Cagrilintide kuj tau pom tias muaj peev xwm tswj cov ntshav qabzib hauv cov neeg mob ntshav qab zib hom 2. Cov kev tshawb fawb soj ntsuam tau qhia tias Cagrilintide nthuav tawm kev ruaj ntseg zoo thiab ua tau zoo hauv kev tswj hwm kev rog thiab hom 2 mob ntshav qab zib. Piv txwv li, hauv kev sim tshuaj ntsuam xyuas nrog rau cov neeg mob ntshav qab zib hom 2, kev sib xyaw ntawm Cagrilintide thiab GLP-1 receptor agonist semaglutide tau tshwm sim zoo kawg li kev tswj ntshav qabzib thiab kev poob phaus. Qhov no qhia tau hais tias Cagrilintide tswj cov qib siab ntawm kev ruaj ntseg hauv kev kho mob thiab muaj peev xwm ua kom muaj txiaj ntsig kho tau zoo. Hauv lwm qhov kev sim tshuaj, Cagrilintide, txawm tias siv ib leeg lossis ua ke nrog semaglutide, tau pom tias muaj kev tiv thaiv zoo thiab kev nyab xeeb ^[8] . Qhov no ntxiv validates kev ruaj ntseg ntawm Cagrilintide, raws li nyob rau hauv kev kho mob daim ntawv thov, kev ruaj ntseg ntawm ib tug tshuaj yog intricately txuam nrog nws tolerability thiab kev nyab xeeb.

Thaum kawg, hauv kev sim tshuaj, kev kho mob nrog cagrilintide tau raug zam zoo. Nyob rau theem 2 kev tshawb nrhiav koob tshuaj, cov nqi ntawm kev kho mob tsis tu ncua tau sib piv thoob plaws ntau pawg kho mob, feem ntau tshwm sim los ntawm cov xwm txheej tsis zoo. Txawm li cas los xij, cov xwm txheej tsis zoo tshwm sim feem ntau yog mob plab hnyuv thiab qhov chaw txhaj tshuaj, nrog rau feem ntau yog mob me mus rau nruab nrab ntawm qhov hnyav. Nyob rau hauv ib qho randomized, tswj theem 1b mus sib hais, cov kev kho mob concurrent nrog cagrilintide thiab 2.4 mg ntawm semaglutide kuj qhia tau hais tias zoo tolerability thiab ib tug txaus kev ruaj ntseg profile ^[9]. Cov kev sim loj dua thiab ntev ntev yuav raug lees paub rau yav tom ntej los ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm kev sib xyaw ua ke no.

Qauv qauv ntawm Cagrinlintide

Source: PubMed ^[5]

Qhov tseem ceeb ntawm kev siv Cagrilintide

Qhov tshwm sim ntawm Cagrilintide tau ua rau muaj kev cia siab tshiab rau kev kho mob rog rog thiab ntshav qab zib hom 2. Txawm hais tias muaj qhov hnyav zuj zus ntawm cov teeb meem kev rog hauv ntiaj teb no, cov kev pom zoo tam sim no rau kev kho tshuaj tseem txwv. Raws li kev ua yeeb yam ntev ntev ntawm amylin analogue, Cagrilintide muab cov kev xaiv kho tshiab rau cov neeg mob rog, tshwj xeeb tshaj yog cov neeg uas muaj cov lus teb tsis zoo rau kev ua neej nyob thiab tsis haum rau kev phais mob bariatric. Nws ua tiav kev tswj hwm qhov hnyav los ntawm kev ua haujlwm tshwj xeeb, muab cov tswv yim tshiab thiab txoj hauv kev rau kev kho mob rog, thiab nws tuaj yeem ua kom pom kev zoo dua thiab kev nyab xeeb piv rau cov tshuaj tiv thaiv kev rog ^[7] . Ntxiv mus, qhov ua tiav ntawm kev sib xyaw ua ke ntawm Cagrilintide thiab semaglutide (CagriSema) qhia tau hais tias kev sib xyaw ua ke ntawm kev kho mob rau ntau lub hom phiaj pathophysiological yog lub tswv yim zoo rau kev txhim kho cov lus teb hauv kev rog ^[8] . Cov qauv kev kho mob ntau lub hom phiaj no tsis yog tsuas yog muab lub ntsiab lus tshiab rau kev tswj hwm kev rog, tab sis kuj tseem coj cov kev txhim kho metabolic tseem ceeb rau cov neeg mob ntshav qab zib hom 2.

Nyob rau hauv xaus, raws li ib tug tshiab ntev-acting amylin analogue, Cagrilintide muaj peev xwm zoo kawg li rau poob phaus thiab tswj ntshav qab zib. 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, siv ib leeg lossis ua ke nrog semaglutide, tuaj yeem txo lub cev hnyav thiab tiv taus zoo. Tsis tas li ntawd, nws kuj tau qhia txog kev tswj cov ntshav qabzib zoo hauv cov neeg mob ntshav qab zib hom 2, muab kev xaiv tshiab rau kev kho mob rog thiab ntshav qab zib mellitus thiab sau qhov sib txawv ntawm cov kev kho mob uas twb muaj lawm, tshwj xeeb tshaj yog rau cov neeg mob uas tsis zoo rau kev ua neej nyob thiab tsis haum rau kev phais. Nws txoj kev kho mob ntau lub hom phiaj muaj kev nkag siab 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 [6].

▎ Cov Lus Qhia Tseem Ceeb

[1] Hansen KE, Murali S, Chaves IZ, Suen G, Ney DM. Glycomacropeptide cuam tshuam rau Amylin-Mediated Satiety, Postprandial Markers ntawm Glucose Homeostasis, thiab Fecal Microbiome nyob rau hauv Obese Postmenopausal Cov Poj Niam. J NUTR 2023; 153(7): 1915-29. DOI: 10.1016/j.tjnut.2023.03.014.

[2] Ling W, Huang Y, Qiao Y, Zhang X, Zhao H. Human Amylin: Los ntawm Pathology mus rau Physiology thiab Pharmacology. CURR PROTEIN PEPT SC 2019; 20(9): 944-57 : kuv. DOI: 10.2174/ 13892037206 66 19032811183 3.

[3] Brunetti L, Recinella L, Orlando G, Michelotto B, Di Nisio C, Vacca M. Cov teebmeem ntawm ghrelin thiab amylin ntawm dopamine, norepinephrine thiab serotonin tso tawm hauv hypothalamus. EUR J PHARMACOL 2002; 454(2-3): 189-92 : kuv. DOI: 10.1016/S0014-2999(02)02552-9.

[4] Gedulin BR, Jodka CM, Herrmann K, Young AA. Lub luag haujlwm ntawm endogenous amylin nyob rau hauv glucagon secretion thiab gastric emptying nyob rau hauv nas tau pom nrog cov xaiv antagonist, AC187. Regulatory Peptides 2006; 137(3): 121-7. DOI: 10.1016/j.regpep.2006.06.004.

[5] Kruse T, Hansen JL, Dahl K, et al. Kev loj hlob ntawm Cagrilintide, Kev Ua Haujlwm Ntev Amylin Analogue. J MED CHEM 2021; 64(15): 11183-94. DOI: 10.1021/acs.jmedchem.1c00565.

[6] Lau DCW, Erichsen L, Francisco AM, et al. Ib zaug ib lub limtiam cagrilintide rau kev tswj qhov hnyav hauv cov neeg uas rog dhau thiab rog: ntau qhov chaw, randomised, ob-dig muag, placebo-tswj thiab nquag-tswj, tshuaj-nrhiav theem 2 mus sib hais. LANCET 2021; 398(10317): 2160-72 : kuv. DOI: 10.1016/S0140-6736(21)01751-7.

[7] D'Ascanio AM, Mullally JA, Frishman WH. Cagrilintide: Ib Lub Sij Hawm Ntev Amylin Analog rau Kev Kho Mob Obesity. CARDIOL REV 2024; 32(1): 83-90 : kuv. DOI: 10.1097/CRD.0000000000000513.

[8] 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 mus sib hais. LANCET 2023; 402(10403): 720-30. DOI: 10.1016/S0140-6736(23)01163-7.

[9] 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. LANCET 2021; 397 (10286): 1736-48. 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.