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ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ Tripul Agonist dɛn
insay di las ia, wit di dip we di risach de dip pan di pathogenesis fכ mεtabolik sik dεm, di divεlכpmεnt fכ mכlti-target agonist dεm we de tכk bכt mכltipכl כmon rεsεpכta dεm dεn bi wan hot tכpik. rεtatrutid na nכvel tripl agonist fכ di glukכs-dipεndεnt insulinotropik pכlipεptida (GIP), glukכn lεk pεptida-1 (GLP-1), εn glukagכn (GC) rεsεpכta dεm.
(1) Fisiolכjik Bεsis fכ di Hכmon Risεptor Fכnshכn Dεm
GIP rεsεptor: GIP na כmon we de kכmכt na di intestinal insulin we di K sεl dεm na di sכmכl intestin de kכmכt, we de kכmכt kwik kwik wan afta dεn it. we i tay to di GIP risεptor, GIP de mek insulin sekreshכn, εn dis stimulatכri ifekt de dipεnd pan glukכs, we min se as di blכd glukכs lεvεl de go כp, GIP de εnhans in insulin-sekret ifekt, we de εp fכ mεnten di blכd glukכs lεvεl stebul. apat frכm dat, GIP de tek pat pan di rεguleshכn fכ di lipid mεtabolism, we de infכlכ di adiposyt difrεns εn lipid akyumyuleshכn.
Fig. 1. RETA ɔ SEMA tritmɛnt de ridyus di bɔdi wet ɛn i de mek di blɔd glukɔs we yu de fast fast.a Dɛn ripɔt pasɛnt chenj na di bɔdi wet frɔm di beslayn. b, Epididymal wayt adipose tisu weit bin kwantifay na di εndpכynt. c Fastin bכdi glukכs bin kwantifay na di beslayn εn tru di stכdi na indikεt tεm pכynt te di εndpכynt. d dεn ripot di tכmכro engraftmεnt כ 'tכmכr tek'.
GLP-1 risεptor: GLP-1 na intestinal L sεl dεm de sekret am εn i gεt bak glukכs-dipεndεnt insulinotropik ifekt, we de εnhans insulin sεntesis εn rilis, inhibit glukagon sekreshכn, εn ridyus hεpatik glukכs autput. GLP-1 de delay bak di gastric ɛmti, i de mek yu satisfay, ɛn dat de mek yu nɔ it bɛtɛ it. i gεt protεktiv εn proliferativ ifekt pan pankrεas beta sεl dεm, we de εp fכ mεnten pankrεas fכ wok.
3. GC Risɛptɔ: .
afta i tay di GC rεsεpכta, glukagon de fכs akt pan di liva bay we i de protεkt glycogenolysis εn gluconeogenesis, we de εlevεt di bכdi glukכs lεvεl. insay lipid mεtabolism, i de protεkt lipolysis, we de inkrεs di rilis εn כksidεshכn fכ fεt asid fכ enεji. כnda nכmal fysiolojikal kכndishכn dεm, di glukכn sekreshכn de inhεbit we di blכd glukכs lεvεl de go כp fכ mεnten di glukכs bεlε.
(2) Advantej dɛn fɔ Tripul Agonist Akshɔn
as tripl agonist, Retatrutid kin aktibכt dεn tri rεsεpכta dεm ya wan tεm, we de εksyεrt sinagεstik ifekt dεm. bay we i de aktibכt GIP εn GLP-1 rεsεpכta dεm, i de εnhans glukכs-dipεndεnt insulin sekreshכn, mכr ifektiv wan lכs di blכd glukכs lεvεl. di inkrεs satiety εn dilay gastric εmpty we GLP-1 rεsεptכr aktibכshכn indyuz, wit di lipolysis we GC rεsεptכr aktibכshכn de protεkt, kכlektivli kכntribyut to wet mεnejmεnt. dis mכlti-targeted mεkanism fכ akshכn de gi mכr kכmprεhεnsiv rεguleshכn fכ difrεn pathophysiological prכsεs dεm we de asai wit mεtabolik sik dεm.
Mekanism fכ akshכn fכ Retatrutid in mεtabolik sik dεm
mεtabolik sik dεm na wan klas כf kכndyushכn dεm we de kכz fכ disrupshכn pan mεtabolik prכsεs insay di bכdi, inklud kכmכn kכndyushכn dεm lεk dayabεtis, fat, εn nכn-alkohol fεt liva sik. Retatrutid de du in ifekt pan dεn mεtabolik sik dεm ya tru in yכnik tripl agonist prכpati dεm.
(1) Mekanism fɔ Akshɔn pan Dayabitis
Glukכs rεgulεshכn: rεtatrutid de aktibכt GIP εn GLP-1 rεsεpכta dεm, we de εnhans glukכs-dipεndεnt insulin sekreshכn. we di glukכs lεvεl dεm na di bכdi go כp, i de mek di pankrεas beta sεl dεm mכr ifektiv fכ sekret insulin, we de mek di glukכs tek εn yutilizeshכn, we de mek di blכd glukכs lεvεl dכn. bay we i de inhibit glukagon sekreshכn εn ridyus di hεpatik glukכs autput, i de stεbyul di bכdi glukכs lεvεl mכr. Insay klinik trayal dɛn we involv pasɛnt dɛn we gɛt tayp 2 dayabitis, di tritmɛnt we dɛn kɔl Retatrutid bin rili ridyus di glukɔs lɛvɛl we dɛn bin de fast ɛn we dɛn bin dɔn it afta dɛn it.
di protεkshכn fכ di pankrεas beta sεl dεm: di aktibכshכn fכ di GLP-1 rεsεpכta nכ de nכmכ de protεkt insulin sekreshכn bכt i de protεktiv εn proliferativ ifekt pan pankrεas beta sεl dεm. rεtatrutid kin achy dis bay we i de kכntinyu fכ aktibכt di GLP-1 rεsεpכta, slo dכn beta sεl apoptosis, inkrεs dεn nכmba εn fכnshכn, we de impruv insulin sekreshכn kapasiti εn mεnten stebul bכdi glukכs lεvεl fכ lכng tεm.
(2) Di we aw pɔsin kin du sɔntin we pɔsin fat pasmak
rεgulεshכn fכ di enεji we yu de it: rεtatrutid de aktibכt di GLP-1 rεsεpכta dεm, i de delay di gεstrik εmpti, i de lכng di tεm fכ rεtεnshכn fכ it na di bεlε, i de mek di it bכku bכku wan, εn i de ridyus di it we i de it. i kin akt pan di sεntri nεv sεstem fכ rεgεl di nyurotransmit dεm we de rilet to di apεtit, lεk fכ inhibit di rilis fכ כreksin, fכ ridyus di apεtit mכr, εn dat de kכntrכl di enεji we i de it.
inkrεs εnεji εkspεndishכn: aktibכshכn fכ di GC rεsεpכta de protεkt lipolysis, inkrεs di rilis εn כksidεshכn fכ fεt asid fכ enεji prodakshכn. di oksidashכn fכ di fεt asid dεm de gi enεji to di bכdi, i de ridyus di fεt we de stכr, εn i de εp fכ lכs di wet. aktibכshכn fכ di GIP rεsεpכta de tek pat bak pan εnεji mεtabolism rεguleshכn, we de inkrεs εnεji εkspεndishכn.
Figure 2 RETA tritmεnt de ridyus di bכdi wet εn adipositi, i de impruv di fastin bכdi glukכs. a Dɛn ripɔt pasɛnt chenj dɛn na di bɔdi wet frɔm di beslayn. b dεn wej di εpididymal wayt adipos tisu na di εndpכynt εn nכmal to tכtal bכdi wet. c Fastin bכdi glukכs bin kwantifay na di beslayn εn tru di stכdi na indikεt tεm pכynt te di εndpכynt.
(3) Mεkanism fכ akshכn insay nכn-alkohol fεt liva sik
impruv di hεpatik lipid mεtabolism: rεtatrutid de aktibכt di GC rεsεpכta, we de protεkt di brεk dכwn εn β-oksidashכn fכ fεt na di liva, we de ridyus fεt akyumyuleshכn na di liva. aktibכshכn fכ di GIP εn GLP-1 rεsεpכta dεm kin rεgεl di εksprεshכn fכ di jin dεm we riliyt to lipid mεtabolism insay di liva, upregulate di εksprεshכn fכ fεt asid transpכrta dεm εn fεt asid כksidayz dεm, we de mek fεt asid כptek εn כksidεshכn, εn fכ impruv di hεpatik lipid mεtabolism mכr.
εnhans insulin sεnsitiviti: pan tap we i de impruv glukכs rεguleshכn εn inkrεs insulin sekreshכn, Retatrutid kin εnhans hεpatik insulin sεnsitiviti bay we i de aktibכt GLP-1 rεsεpכta dεm. di εnhans insulin sεnsitiviti de εnhans di liva in rεspכns to insulin, bεtε inhεbit di hεpatik glukכs autput, ridyus di de novo fεt asid sεntesis, εn dat de mek di hεpatik stεatosis bεtε.
Aplikeshɔn ɛn Ifɛkt dɛn we Retatrutid gɛt pan Mɛtabolik sik dɛn
(1) Aw fɔ yuz am pan Dayabitis
lycemic Control Effects: Retatrutid de sho signifyant glycemic kontrכl ifekt dεm pan pasεn dεm we gεt tayp 2 dayabεtis. Akɔdin to di data, di pasɛnt dɛn we dɛn trit wit Retatrutid sho se di ɛmoglobin A1c (HbA1c) lɛvɛl dɔn ridyus bad bad wan. Insay wan randomized kɔntrol trayal we involv 353 pasɛnt dɛn we gɛt tayp 2 dayabitis, di HbA1c lɛvɛl dɛn na di Retatrutid tritmɛnt grup bin go dɔŋ bay 1.64% frɔm di beslayn, we nɔ bin gɛt ɛni impɔtant chenj na di plesibo grup.
Kכmpεre wit כda Drug dεm: We yu kכmpεr wit tradishכnal antidiabetic drog dεm lεk mεtformin כ GLP-1 rεsεptכr agonist, Retatrutid de sho se i gεt supεriכr bכdi glukכs kכntrכl ifekt dεm.
(2) Aplikeshɔn pan pɔsin we fat
Di ifɛkt dɛm we pɔsin kin gɛt we i de lɔs di wet: Retatrutid de sho se i ebul fɔ trit pɔsin we fat pasmak. Insay klinik trayal dɛn we dɛn bin de tɔch big pipul dɛn we fat, dɛn bin si se dɛn dɔn lɔs bɔku bɔku wet afta 48 wiks we dɛn bin de trit dɛn wit difrɛn doz dɛn fɔ Retatrutid. Insay wan trayal, di pasɛnt dɛn we dɛn trit wit 12mg doz fɔ Retatrutid bin gɛt avɛj wet lɔs we na 24.2% afta 48 wik, we yu kɔmpia am wit 2.1% nɔmɔ na di plesibo grup. Apat frɔm dat, 83% pan di patisipan dɛn na di ay-dos grup bin ajɔst di wet lɔs we na 15% ɔ mɔ, we pas di 2% rit na di plasɛbo grup fa fawe.
Lɔng Tɛm Ifekt: Retatrutid de mentɛn di weit lɔs ifɛkt fayn fayn wan ɔl di tɛm we dɛn de trit am. Dis sho se if yu yuz am fɔ lɔng tɛm, dat kin ɛp fɔ mek yu gɛt stebul wet ɛn mek yu nɔ gɛt mɔ wet bak, we go bɛnifit yu fɔ mɛn yu fat fɔ lɔng tɛm.
(3) Aplikeshɔn insay nɔ-alkohol fat liva sik
Liva fat ridyushɔn: Insay pasɛnt dɛn we gɛt mɛtabolik disfɔkshɔn-asɔsiet fat liva sik ɛn liva fat kɔntinyu ≥10%, Retatrutid tritmɛnt rizulta in signifyant ridɔkshɔn pan liva fat kɔntinyu. Insay wan randomiz, dɛbul-blaynd, plesibo-kɔntrol trayal, na 24 wik, di liva fat kɔntinyu fɔ go dɔŋ bay 81.4% ɛn 82.4% frɔm di beslayn insay di 8 mg ɛn 12 mg doz grup dɛn, rispɛktvɔli, we di plesibo grup inkrisayz bay 0.3% nɔmɔ.
Advantej ɛn Potensial fɔ di Tripul Agonist
rεtatrutid kכmprεhεnsivli rεgεl mכltipכl patכfysiolojikal path dεm fכ mεtabolik sik dεm bay we i de aktibכt GIP, GLP-1, εn GC rεsεpכta dεm wan tεm. frכm blכd glukכs kכntrכl, weit mεnejmεnt, to impruv hεpatik lipid mεtabolism, dis mכlti-tכgεt mεkanism fכ akshכn tiori wan de gi mכr kכmprεhεnsiv kכrekshכn fכ mεtabolik dizכrd dεm we yu kכmpεr to singl-target drog dεm, we de sho pכtεnshal fכ adrεs di kכmpleks etioloji fכ mεtabolik sik dεm. Di klinik trial data we de naw sho se Retatrutid dɔn ajɔst bɔku ifɛkt dɛn pan di tritmɛnt fɔ mɛtabolik sik dɛn lɛk dayabitis, fat, ɛn nɔ-alkohol fat liva sik.
Dɔn
As wan nyu triplɛ agonist, Retatrutid gɛt prɔmis fɔ di tritmɛnt fɔ mɛtabolik sik dɛn.
Sos dɛn we dɛn pul
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[2] Kaur M, Misra S. Wan rivyu fɔ wan invɛstigeshɔn drɔg retatrutide, wan nyu tripl agonist ɛjɛn fɔ di tritmɛnt fɔ ɔbisiti[J]. Yuropian Jɔnal fɔ Klinik Famakɔlɔji, 2024,80(5):669-676.DOI:10.1007/s00228-024-03646-0.
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Prodak we de fɔ yuz fɔ risach nɔmɔ:
