▎ Survodutide Kev Tshawb Fawb
Kev tshawb fawb keeb kwm ntawm Survodutide yog dab tsi?
Prevalence ntawm Metabolic Disease:
Nrog rau kev nrawm nrawm ntawm lub neej thiab kev hloov pauv ntawm cov qauv kev noj haus, cov kab mob metabolic xws li rog rog, hom 2 mob ntshav qab zib mellitus, thiab tsis muaj dej cawv steatohepatitis (NASH) tau dhau los ua kev nyuaj rau kev noj qab haus huv thoob ntiaj teb. Piv txwv li, qhov tshwm sim ntawm metabolic-associated fatty siab kab mob (MAFLD) ntau dua 30%, thiab nws tau kwv yees tias los ntawm 2030, metabolic dysfunction-associated steatohepatitis (MASH) yuav dhau los ua qhov tseem ceeb ntawm kev hloov lub siab, ua rau lub nra hnyav rau kev noj qab haus huv.
Kev txwv ntawm cov tshuaj uas twb muaj lawm:
Cov tshuaj GLP-1 ib txwm muaj qee yam kev txwv hauv kev kho cov kab mob metabolic. Rau qee tus neeg mob, qhov kev poob phaus tsis txaus siab, lossis lawv tuaj yeem ntsib kev mob plab hnyuv. Ntxiv mus, lawv lub peev xwm los txhim kho daim siab rog metabolism yog txwv, thiab kev kam rau siab tuaj yeem txhim kho nrog kev siv mus ntev.
Qhov zoo ntawm Dual Agonists:
Raws li ib tug dual agonist ntawm glucagon-zoo li peptide-1 receptor (GLP-1R) thiab glucagon receptor (GCGR), Survodutide tuaj yeem tswj cov metabolism hauv ntau qhov ntev. Los ntawm txoj kev GLP-1R, nws tuaj yeem txo qis qab los noj mov, ncua kev ua pa hauv plab, thiab txhawb nqa cov tshuaj insulin kom txo cov ntshav qabzib. Los ntawm txoj kev GCGR, nws tuaj yeem txhim kho fatty acid oxidation nyob rau hauv daim siab, txo cov rog, thiab ncaj qha txhim kho daim siab fibrosis, ua kom pom cov txiaj ntsig zoo ntawm kev rog rog, ntshav qab zib, thiab kab mob siab hauv cov tsiaj sim.
Lub mechanism ntawm kev txiav txim ntawm Survodutide yog dab tsi?
1. Dual Receptor Agonism
Survodutide yog ob agonist ntawm glucagon receptor (GCGR) / glucagon-zoo li peptide-1 receptor (GLP-1R).
GLP-1R AGONism
Tom qab ua haujlwm ntawm GLP-1 receptor, nws tuaj yeem txhim kho cov piam thaj-dependent insulin secretion thiab inhibit glucagon secretion, yog li txo cov ntshav qabzib. Thaum Survovudutide activates GLP-1R, nws tuaj yeem txhawb nqa insulin secretion los ntawm pancreatic islet β hlwb thiab, tib lub sijhawm, txo glucagon secretion los ntawm pancreatic islet α hlwb, ua tiav kev tswj hwm ntawm cov ntshav qabzib zoo [1].
Tsis tas li ntawd, GLP-1R agonism kuj tseem tuaj yeem ncua lub plab zom mov thiab ua kom lub siab puv, yog li pab txo qis kev noj zaub mov thiab tswj lub cev hnyav.
GCGR Agonism
Ua kom cov glucagon receptor tuaj yeem ua kom lub zog noj thiab txhawb kev rog rog. Survodutide nkoos GCGR, ua rau lub cev lub zog metabolism hauv theem thiab ua rau kev ua txhaum ntawm triglycerides hauv cov ntaub so ntswg adipose mus rau hauv fatty acids thiab glycerol, muab lub zog rau lub cev [1].
2. Cov teebmeem ntawm Metabolism
Txhim kho Glucose Metabolism
Survovudutide txo qis qib ntawm glycated hemoglobin (HbA1c). Hauv kev tshawb fawb soj ntsuam, cov neeg mob ntshav qab zib hom 2 tau kho nrog Survovudutide pom qhov txo qis hauv qib HbA1c tom qab 16 lub lis piam kho. Piv txwv li, piv nrog semaglutide, cov koob tshuaj qis Survovudutide (DG2) muaj cov nyhuv zoo sib xws hauv kev txo HbA1c. Cov qib HbA1c hauv pawg DG2 poob qis los ntawm 15.95 mmol / mol (-1.46%), thaum nyob hauv pawg semaglutide poob los ntawm 16.07 mmol / mol (-1.47%) [1].
Nws cov txheej txheem ntawm kev ua haujlwm tuaj yeem ua tiav los ntawm kev txhim kho cov tshuaj insulin secretion, inhibiting glucagon secretion, thiab txhim kho kev nqus thiab siv cov piam thaj los ntawm cov ntaub so ntswg peripheral.
Kev tswj ntawm Lipid Metabolism
Survovudutide tuaj yeem txo cov ntshav lipid. Hauv kev tshawb fawb ntawm cov neeg mob rog rog, piv nrog cov placebo, Survodutide txo qis triglyceride (TG) qib, thiab kuj txo qis cov lipoprotein tsawg (LDL), tag nrho cov roj (TC), thiab cov roj lipoprotein tsis-siab (tsis-HDL-C) hauv qee pawg koob tshuaj [2].
Nyob rau tib lub sijhawm, Survodutide tuaj yeem txo cov rog hauv siab. Hauv kev tshawb fawb ntawm cov neeg mob uas muaj metabolic dysfunction-associated steatohepatitis (MASH), qhov feem pua ntawm cov neeg mob kho nrog Survovudutide uas nws lub siab rog cov ntsiab lus txo tsawg kawg yog 30% yog qhov siab dua li cov placebo pawg. Piv txwv li, 63%, 67%, thiab 57% ntawm cov neeg mob hauv Survovudutide 2.4mg, 4.8mg, thiab 6.0mg pawg, raws li, tau mus txog qhov ntsuas no, thaum tsuas yog 14% hauv pawg placebo [3].
3. Kev cuam tshuam rau cov hlab plawv
Kev txhim kho cov kab mob plawv
Survovudutide tuaj yeem txo cov ntshav siab. Hauv cov neeg mob rog rog, piv nrog cov placebo, ob qho tib si systolic ntshav siab (SBP) thiab diastolic ntshav siab (DBP) txo qis tom qab kho nrog Survodutide. Hauv kev kho mob tiag tiag, Survodutide tuaj yeem txo SBP txog li 10.2 mmHg thiab DBP los ntawm 4.8 mmHg, thiab cov ntshav siab txo qis zoo ib yam txawm hais tias tus neeg mob puas muaj ntshav siab ua ntej kuaj [2].
Tsis tas li ntawd, Survodutide tuaj yeem txo lub duav ncig. Hauv cov neeg mob rog rog, lub duav ncig ntawm cov neeg mob hauv txhua pawg Survodutide koob tshuaj txo qis, thiab 4.8mg pawg tau txo qis tshaj plaws, uas yog 16.6 cm [2].
Cov txiaj ntsig ntawm Cov Cim Ntawm Tsis-alcoholic Steatohepatitis (NASH)
Survovudutide tej zaum yuav muaj kev txhim kho ntawm qee cov cim ntawm cov tsis-alcoholic steatohepatitis (NASH). Cov kev tshawb fawb tam sim no qhia tias Survodutide tuaj yeem ua lub luag haujlwm hauv inhibiting kev loj hlob ntawm NASH los ntawm kev txhim kho daim siab rog metabolism thiab lub xeev inflammatory [4].
Dab tsi yog cov ntawv thov ntawm Survodutide?
1. Kev kho mob ntawm hom 2 mob ntshav qab zib mellitus thiab rog rog
Raws li kev ua haujlwm ntev ntev dual agonist, Survodutide tau muab tshuaj ib zaug ib lub lim tiam thiab tau pom cov teebmeem tseem ceeb hauv kev kho mob ntawm hom 2 mob ntshav qab zib mellitus (T2DM) thiab rog rog.
Kev txo qis ntawm glycated hemoglobin (HbA1c):
Ntau qhov kev sim tshuaj tau pom tias Survodutide tuaj yeem txo qis HbA1c hauv cov neeg mob. Piv txwv li, hauv kev tshawb fawb ntawm cov neeg mob T2DM, tom qab 16 lub lis piam ntawm kev kho mob, qib HbA1c txo qis mus txog 1.7% [4] . HbA1c yog ib qho tseem ceeb qhia txog kev tswj cov ntshav qabzib mus ntev, thiab nws qhov txo qis txhais tau tias tus neeg mob cov ntshav qabzib tswj tau zoo dua.
Tseem ceeb poob phaus:
Rau cov neeg mob uas muaj T2DM thiab rog rog, Survodutide tuaj yeem ua tiav qhov hnyav txog li 14.9% thaum 46 lub lis piam kho mob [4] . Qhov no yog ib qho tseem ceeb heev rau cov neeg mob uas muaj teeb meem los ntawm qhov hnyav nce feem ntau tshwm sim los ntawm cov tshuaj antidiabetic. Kev poob phaus tsis tsuas yog pab txhim kho tus neeg mob lub ntsej muag thiab lub neej zoo, tab sis kuj txo qhov kev pheej hmoo ntawm cov teeb meem xws li kab mob plawv.
2. Kev txhim kho cov kab mob plawv
Survodutide kuj muaj qhov cuam tshuam zoo rau cov kab mob plawv.
Ntshav Qab Zib:
Hauv kev sim tshuaj ntawm cov neeg mob rog rog, piv nrog cov placebo, Survodutide tuaj yeem txo cov ntshav siab txog li 10.2 mmHg thiab diastolic ntshav siab los ntawm 4.8 mmHg [2] . Kev txo cov ntshav siab yog qhov tseem ceeb heev rau kev tiv thaiv kab mob plawv, tshwj xeeb tshaj yog rau cov neeg mob rog rog thiab kub siab.
Txhim kho cov ntshav lipid Parameters:
Survodutide tuaj yeem txo cov qib triglyceride (TG) thiab tseem muaj qee yam kev txhim kho ntawm cov ntshav lipid tsis xws li high-density lipoprotein (HDL), low-density lipoprotein (LDL), tag nrho cov cholesterol (TC), thiab tsis-high-density lipoprotein cholesterol (non-HDL-C) [2] . Piv txwv li, hauv kev npaj kho mob, qhov nruab nrab TG hauv txhua pawg Survodutide poob qis heev.
3. Kev kho mob tsis muaj dej cawv Steatohepatitis (NASH)
Survodutide kuj tseem qhia tau tias muaj peev xwm hauv kev kho mob tsis muaj cawv steatohepatitis (NASH).
Txhim kho daim siab Histology:
Hauv 48-lub lim tiam, theem 2 kev soj ntsuam ntawm cov neeg laus cov neeg mob nrog MASH (metabolic dysfunction-associated steatohepatitis) thiab daim siab fibrosis, Survodutide yog superior rau cov placebo hauv kev txhim kho MASH yam tsis ua rau daim siab fibrosis. Tshwj xeeb, ntawm cov neeg mob kho nrog ntau koob tshuaj Survodutide, 47% ntawm cov neeg mob hauv pawg 2.4mg, 62% ntawm cov neeg mob hauv pawg 4.8mg, thiab 43% ntawm cov neeg mob hauv pawg 6.0mg tau pom kev txhim kho hauv MASH, thaum tsuas yog 14% hauv pawg placebo [3].
Kev txo qis ntawm daim siab rog cov ntsiab lus:
Survodutide kuj tseem tuaj yeem txo cov rog hauv siab. Hauv kev sim tshuaj ntsuam xyuas saum toj no, 63%, 67%, thiab 57% ntawm cov neeg mob kho nrog 2.4mg, 4.8mg, thiab 6.0mg koob ntawm Survodutide, raws li, tau txo qis hauv siab rog cov ntsiab lus tsawg kawg yog 30%, thaum tsuas yog 14% hauv pawg placebo [3].
Txhim kho daim siab Fibrosis:
Tsis tas li ntawd, nws tau txhim kho daim siab fibrosis rau qee yam. Hauv qhov kev sim no, 34%, 36%, thiab 34% ntawm cov neeg mob tau kho nrog 2.4mg, 4.8mg, thiab 6.0mg koob tshuaj Survodutide, raws li, pom tau tias muaj kev txhim kho hauv daim siab fibrosis tsawg kawg ib theem, thaum nws yog 22% hauv cov placebo pawg [3].
4. Kev cuam tshuam rau kev nyiam noj zaub mov thiab txhim kho Dyslipidemia
Hauv cov qauv rog rog, ob qho tib si Survodutide thiab lwm yam tshuaj, Semaglutid, tuaj yeem ua rau poob phaus thiab txo cov tshuaj insulin tsis kam (HOMA-IR), tab sis lawv muaj qhov sib txawv ntawm cov khoom noj nyiam thiab dyslipidemia.
Qhov cuam tshuam rau kev noj zaub mov:
Semaglutid txo qis kev noj zaub mov tsis tu ncua thiab muaj roj ntau hauv thawj lub lim tiam ntawm kev kho mob tab sis tom qab ntawd rov qab mus rau tus nqi pib. Nyob rau tib lub sijhawm, nws nce qhov kev noj haus ntawm cov dej ib txwm muaj thiab txo cov dej ntau ntawm fructose. Hauv qhov sib piv, Survodutide tsis tau hloov pauv kev noj zaub mov tsis tu ncua thiab dej ib txwm muaj tab sis txo qis kev noj cov rog rog thiab cov dej nplua nuj fructose thaum lub sijhawm kho 5 lub lis piam [5].
Cov txiaj ntsig ntawm cov ntshav lipids:
Ob leeg Semaglutid thiab Survodutide tuaj yeem txo cov ntshav plasma tag nrho cov roj cholesterol, nrog kev txo qis ntawm 24% thiab 41%, feem. Kev txo qis ntawm tag nrho cov roj cholesterol los ntawm Semaglutid coj mus rau 25% txo qis hauv cov roj lipoprotein cholesterol siab, tab sis cov qib lipoprotein cholesterol tsawg tsis hloov. Kev txo cov roj cholesterol ntawm Survodutide tau pom nyob rau hauv tag nrho cov lipoprotein Cheebtsam, suav nrog 39% txo qis lipoprotein cholesterol [5].
Hauv kev xaus, raws li ib tug dual receptor agonist, Survodutide tuaj yeem tswj cov metabolism, txo cov ntshav qabzib, txo lub cev hnyav, txhim kho cov kab mob plawv, thiab txhim kho cov cim ntawm cov tsis muaj cawv steatohepatitis. Nws muab cov tswv yim tshiab rau kev kho mob ntsig txog kab mob thiab tseem ceeb heev rau kev txhim kho qib kev noj qab haus huv ntawm cov neeg 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
Le Roux C yog tus kws tshawb fawb koom nrog ntau lub koom haum. Cov no suav nrog University College Dublin, St Vincents Uni Hosp, Ulster University, Saint Vincent's University Tsev Kho Mob, St Vincents Hosp Grp, KU Leuven, Tsev Kho Mob Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, University of Gothenburg, Imperial College London, ICL, Univ Dublin, Istituto per la Sintetes (ISOF-CNR), Maastricht University, King's College Hospital, King's College Hospital NHS Foundation Trust, Musgrove Park Hospital thiab National Hospital for Neurology & Neurosurgery.
Nws cov kev xav tau kev tshawb fawb muaj ntau yam, suav nrog Kev phais, Endocrinology & Metabolism, Khoom noj khoom haus & Dietetics, Oncology, thiab Biochemistry & Molecular Biology. Nws txoj haujlwm nyob rau hauv cov cheeb tsam no qhia tau hais tias nws cov kev txawj ntse thiab cov txiaj ntsig tseem ceeb uas nws tau ua rau kev nce qib ntawm kev kho mob science. Le Roux C tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [2].
