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1 khoom (10Vials)
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▎ Mazdutide Structure
Source: PubChem |
Sequence: AEGTFTSDVSSYLEGQAAKFIAWLVKGRG Molecular Formula: C 207H 317N 45O65 Molecular Luj: 4476g/mol CAS Nr .: 2259884-03-0 PubChem CID: 167312357 Cov ntsiab lus: GLXC-26803 |
▎ Mazdutide Kev Tshawb Fawb
Kev tshawb fawb keeb kwm ntawm Mazdutide yog dab tsi?
Qhov teeb meem tseem ceeb ntawm kev rog thoob ntiaj teb thiab cov kab mob ntsig txog:
Kev rog dhau thiab rog tau dhau los ua kev nyuaj rau kev noj qab haus huv thoob ntiaj teb. Raws li World Obesity Atlas, tus naj npawb ntawm cov neeg rog rog thoob ntiaj teb tau mus txog 764 lab hauv 2020 thiab xav tias yuav nce mus txog 1 billion los ntawm 2030. Kev rog rog tuaj yeem ua rau muaj teeb meem kev noj qab haus huv ntau, xws li kab mob plawv thiab ntshav qab zib hom 2, uas cuam tshuam rau tib neeg lub neej thiab kev kho mob thoob ntiaj teb. Qhov no tau tsav cov kws tshawb fawb los tshawb nrhiav cov kev kho mob zoo, tshwj xeeb tshaj yog cov tshuaj tshiab.
Kev txhim kho hauv paus ntawm cov tshuaj incretin-based:
Txij li thaum lub tswv yim ntawm incretin tau tawm tswv yim hauv xyoo 1932, cov kev tshawb fawb ntsig txog tau nce mus tas li. Hauv xyoo 1987, GLP-1 tau raug txheeb xyuas tias yog tus tswj hwm tseem ceeb ntawm kev tso cov tshuaj insulin hauv lub txiav, thiab kev kho mob rau hom 2 mob ntshav qab zib mellitus raws li incretin tau tsim. Hauv xyoo 2005, exenatide, lub ntiaj teb thawj GLP-1 receptor agonist (GLP-1RA), tau pom zoo rau kev lag luam, tso lub hauv paus zoo rau kev tshawb fawb thiab kev tsim cov tshuaj incretin-raws li Mazdutide. Mazdutide yog ib qho analog ntawm mammalian oxyntomodulin (OXM). Raws li ib tug tshiab tiam tshiab dual agonist tsom GLP-1R thiab GCGR, nws muaj ib tug tshwj xeeb dual-txoj kev mechanism thiab broad zeem muag nyob rau hauv kev kho mob ntawm yuag poob thiab lwm yam kab mob.
Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm Mazdutide?
Agonistic nyhuv ntawm glucagon-zoo li peptide-1 (GLP-1) receptor:
GLP-1 yog ib qho tshuaj hormones hauv plab uas tuaj yeem txhawb nqa cov tshuaj insulin secretion thiab inhibit glucagon secretion hauv cov piam thaj hauv cov ntshav, yog li txo cov ntshav qabzib [1] . Raws li GLP-1 receptor agonist, Mazdutide ua raws li kev ua ntawm GLP-1, txhim kho insulin tso tawm thiab txo qis glucagon tso tawm, uas pab tswj cov ntshav qabzib. Ntxiv mus, GLP-1 receptor agonists tuaj yeem ncua lub plab zom mov, txhim kho satiety, thiab txo cov zaub mov noj, uas muaj txiaj ntsig zoo rau kev tswj qhov hnyav [1, 2].
Cov nyhuv agonistic ntawm glucagon receptor:
Glucagon tuaj yeem txhawb kev tawg ntawm daim siab glycogen thiab gluconeogenesis, ua rau nce ntshav qabzib. Mazdutide, los ntawm kev ua kom cov glucagon receptor, tuaj yeem tswj ntau yam ntawm cov piam thaj metabolism, ua tiav kev tswj hwm cov ntshav qabzib. Glucagon tseem txhawb nqa lipolysis, pab txo cov rog thiab txo lub cev hnyav [1, 2].
Regulatory nyhuv ntawm ntshav siab:
Mazdutide tuaj yeem txo cov ntshav siab systolic thiab diastolic. Ntawm ib sab, nws txo cov ntshav siab los ntawm kev tswj cov piam thaj thiab lipid metabolism thiab txhim kho vascular endothelial muaj nuj nqi; Ntawm qhov tod tes, nws tuaj yeem cuam tshuam cov kev tswj ntshav siab xws li renin-angiotensin system.
Dab tsi yog qhov tshwj xeeb mechanism ntawm Mazdutide rau kev poob phaus?
Kev tswj cov ntshav qabzib thiab cov metabolism hauv:
Raws li ib tug dual agonist ntawm glucagon-zoo li peptide-1 (GLP-1) thiab glucagon receptors, ib qho ntawm ntau yam physiological teebmeem ntawm GLP-1 yog los tswj cov ntshav qabzib. Nws txhawb nqa insulin secretion, inhibits glucagon secretion, txo cov ntshav qabzib [1] , qeeb plab hnyuv, ua kom satiety, thiab txo cov zaub mov noj. Glucagon, ntawm qhov tod tes, txhawb lipolysis thiab kev siv zog. Yog li, Mazdutide activates ob receptors thiab tswj cov ntshav qabzib metabolism kom ua tiav qhov hnyav. Cov kev tshawb fawb tau pom tias Mazdutide tuaj yeem txo lub cev hnyav, ntshav siab (systolic thiab diastolic), tag nrho cov roj cholesterol, triglycerides, lipoprotein tsawg ntom ntom, thiab cov lipoprotein ntau ntom ntom [3] , qhia tias nws tuaj yeem ua rau poob phaus thiab txhim kho kev rog rog ntsig txog metabolic.
Influence on qab los noj mov thiab lub zog noj:
Mazdutide tuaj yeem ua tiav qhov poob phaus los ntawm kev cuam tshuam kev qab los noj mov thiab lub zog kom tsawg. Hauv qee qhov kev sim tshuaj, cov neeg tuaj koom tau ntsib kev mob plab hnyuv xws li txo qis qab los noj mov tom qab siv Mazdutide [3] . Qhov no tej zaum yuav tshwm sim los ntawm qhov ncaj qha kev txiav txim ntawm Mazdutide ntawm lub plab zom mov los yog los ntawm kev tswj hwm los ntawm lub hauv paus paj hlwb. Tsis hais txog ntawm cov txheej txheem, qhov tsis qab los noj mov thiab kev mob plab zom mov yuav txo tau lub zog kom tsawg thiab txhawb kev poob phaus. Tsis tas li ntawd, Mazdutide tuaj yeem cuam tshuam kev noj qab haus huv los ntawm kev tswj cov neurotransmitters thiab cov tshuaj hormones hauv lub hlwb. Piv txwv li, GLP-1 tuaj yeem ua rau ntawm hypothalamus los tswj kev qab los noj mov thiab lub zog sib npaug [4].
Dab tsi yog txoj hauv kev tshwj xeeb ntawm Mazdutide hauv kev tswj cov ntshav qabzib?
Stimulation ntawm insulin secretion:
Glucagon-zoo li peptide-1 (GLP-1) receptor agonists tuaj yeem txhawb nqa cov tshuaj insulin. Raws li ib tug dual agonist ntawm GLP-1 thiab glucagon receptors, Mazdutide tuaj yeem qhib GLP-1 receptor kom ua rau pancreatic islet β hlwb kom zais cov tshuaj insulin. Insulin yog cov tshuaj hormones tseem ceeb los txo cov ntshav qabzib, uas tuaj yeem txhawb cov hlwb kom noj qabzib thiab txo cov ntshav qabzib ntau [1].
Inhibition ntawm glucagon secretion:
Tib lub sijhawm, Mazdutide tuaj yeem ua rau glucagon receptor inhibition glucagon secretion. Glucagon thiab insulin yog qhov tsis sib haum xeeb rau ib leeg hauv kev tswj cov ntshav qabzib, thiab txo qis nws qhov tso tawm yog qhov tsim nyog rau kev txo qis ntshav qabzib [1].
Kev tswj cov piam thaj metabolism:
Mazdutide tuaj yeem tswj hwm cov piam thaj metabolism hauv ntau qib kom ua rau nws cov nyhuv hypoglycemic, xws li cuam tshuam rau cov piam thaj metabolism hauv daim siab, cov leeg, thiab cov ntaub so ntswg adipose. Nyob rau hauv daim siab, nws txo qhov kev puas tsuaj ntawm daim siab glycogen thiab gluconeogenesis, txo cov ntshav qabzib; nyob rau hauv cov leeg nqaij, nws txhawb nqa thiab siv cov piam thaj; Nyob rau hauv cov ntaub so ntswg adipose, nws tswj lipid metabolism, txo qhov tso tawm ntawm cov rog dawb, thiab tsis ncaj qha cuam tshuam rau cov ntshav qabzib [1, 3].
Influence on qab los noj mov thiab lub zog noj:
Cov kev tshawb fawb tau pom tias Mazdutide tuaj yeem txo qhov qab los noj mov thiab lub zog noj, tej zaum los ntawm kev ua ntawm cov receptors hauv nruab nrab paj hlwb thiab tswj txoj kev qab los noj mov. Txo cov zaub mov kom tsawg tuaj yeem txo cov ntshav qabzib thiab pab tswj cov ntshav qabzib ntau [3, 5].
Hloov ntawm lub hauv paus hauv lub cev qhov hnyav thiab lub duav ncig.
a.Percent hloov ntawm lub hauv paus hauv lub cev hnyav dhau sijhawm. b. Hloov ntawm lub hauv paus hauv lub cev hnyav dhau sijhawm.
Source: PubMed [2]
Dab tsi yog cov ntawv thov ntawm Mazdutide?
Kev kho mob ntshav qab zib hom 2:
Ib qho randomized, ob-dig muag, placebo-tswj Theem 2 qhov kev sim pom tau tias Mazdutide, ib lub limtiam-tswj dual agonist ntawm glucagon-zoo li peptide 1 (GLP-1) thiab glucagon receptors, ua tau zoo thiab kev nyab xeeb hauv Suav cov neeg mob ntshav qab zib hom 2 [1].
Daim ntawv thov hauv kev poob phaus:
Kev tshawb fawb ntawm cov neeg mob thiab tsis muaj ntshav qab zib: Kev tshuaj xyuas thiab kev tshuaj ntsuam xyuas tau pom tias Mazdutide tuaj yeem txo lub cev hnyav ntawm cov neeg laus uas muaj lossis tsis muaj ntshav qab zib [3] . Cov kev tshawb fawb no suav nrog xya qhov kev sim tswj kev sim nrog tag nrho ntawm 680 tus neeg koom. Cov txiaj ntsig tau pom tias piv nrog cov placebo, Mazdutide ua rau txo qis hauv lub cev hnyav dua (txhais tau qhov sib txawv [MD] = -6.22%, 95% kev ntseeg siab lub sijhawm [CI]: -8.02% rau -4.41%, I⊃2; = 90.0%) (Nalisa DL, 2024). Cov pab pawg thiab meta-regression tsom xam pom tias cov neeg mob uas tsis muaj ntshav qab zib tau poob qhov hnyav dua, thiab cov neeg mob tau kho rau 24 lub lis piam tau txo qhov hnyav dua piv rau cov uas tau kho rau 12 - 20 lub lis piam [3].
Daim ntawv thov hauv Suav cov neeg laus uas rog dhau lossis rog:
Ib nrab-lub sij hawm tsom xam ntawm ib tug randomized, ob-feem (tsawg koob mus txog 6mg thiab siab koob tshuaj 9mg), ob-dig muag, placebo-tswj Phase 2 sim ua nyob rau hauv Suav cov neeg laus uas rog rog los yog rog pom tau hais tias Mazdutide muaj kev nyab xeeb thiab siv tau nyob rau hauv cov pejxeem no thaum lub sij hawm 24-lub lim tiam kho mob, nqa txog qhov hnyav thiab poob 2 lub ntsiab lus . Hauv txoj kev tshawb no, cov neeg laus uas rog dhau (BMI ≥ 24 kg / m²) nrog hyperphagia thiab / lossis tsawg kawg yog ib qho kev rog rog, lossis cov neeg laus rog rog (BMI ≥ 28 kg / m²) tau randomly tau txais Mazdutide txhua lub lim tiam ntawm qhov chaw ntawm koob tshuaj 4 mg, 5 mg. Cov txiaj ntsig tau pom tias los ntawm lub hauv paus pib mus rau 24 lub lim tiam, qhov feem pua ntawm lub cev hloov pauv yog -6.7% (tus qauv yuam kev 0.7) hauv 3mg Mazdutide pawg, -10.4% (0.7) hauv 4.5mg pawg, -11.3% (0.7) hauv 6mg pawg, thiab 0.7% ntawm pawg. Piv nrog rau cov placebo, qhov kev kho mob txawv ntawm -7.7% mus rau -12.3% (tag nrho p <0.0001) [2].
Hauv kev xaus, raws li lub tswv yim tshiab dual-target agonist, los ntawm ntau lub tswv yim xws li tswj cov ntshav qabzib, txhawb kev rog metabolism, thiab inhibiting qab los noj mov, Mazdutide tuaj yeem txhim kho cov ntshav qabzib ntawm cov neeg mob ntshav qab zib hom 2 thiab pab cov neeg rog rog poob phaus. Nws txhaj tshuaj tshiab tseem ceeb rau hauv kev kho mob ntawm cov kab mob metabolic thiab xav tias yuav txo tau lub nra thoob ntiaj teb ntawm kev rog rog thiab lwm yam kab mob.
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
Zhang B yog ib tus kws tshaj lij uas muaj peev xwm txuas nrog ntau lub koom haum muaj npe nrov. Cov no suav nrog Peking Union Medical College, Suav Academy ntawm Kev Kho Mob Sciences -Peking Union Medical College, - Nyiv Tsev Kho Mob Friendship, Guizhou Equipment Mfg Polytech, Shanghai Jiao Tong University, Universiti Utara Malaysia, Yingkou Institute of Technology, Zhejiang University, thiab Peking Union Medical College Tsev Kho Mob. Cov kev sib txawv ntawm cov koom haum sib txawv no qhia txog nws txoj kev kawm dav dav thiab kev tshawb fawb keeb kwm yav dhau los.
Hais txog kev tshawb fawb, Zhang B muaj ntau yam kev kawm. Nws cov kev txawj ntse suav nrog Endocrinology & Metabolism, General & Internal Medicine, Oncology, Cardiovascular System & Cardiology, thiab Radiology, Nuclear Medicine & Medical Imaging. Nws txoj haujlwm hauv cov haujlwm no qhia txog nws qhov kev paub tob tob thiab muaj txiaj ntsig tseem ceeb rau kev nce qib kev kho mob thiab kev txhim kho kev noj qab haus huv. Zhang B tau teev nyob rau hauv kev siv ntawm cov ntaub ntawv pov thawj [1].
