Na Cocer Peptides bin rayt am 
2 mɔnt dɔn pas
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.
As di sik dɛm wae de kam pan mɛtabolik lɛk fɔ gɛt pasmak bɔdi, fɔ fat pasmak, ɛn fɔ gɛt dayabitis de kɔntinyu fɔ bɔku ɔlsay na di wɔl, fɔ fɛn mɔr ɛfifishin mɛrɛsin dɛm fɔ mɛn pipul dɛm dɔn bi wan hot tɔpik na di mɛdikal fild. Mazdutide, as nכvel dual rεsεpכta agonist, kin aktibכt di GLP-1 rεsεpכta εn di glukagon rεsεpכta wan tεm, εn dεn de εkspεkt fכ ple wan yכnik rol fכ lכs weit εn blכd shuga kכntrכl, we de gi nyu chans fכ trit mεtabolik sik dεm.
Figure 1 Di kεmikכl strכkchכ fכ Mazdutide.
Ovaviu fɔ Mazdutide
Mazdutide na GLP-1/glucagon dual receptor agonist, we na wan nyu drɔg fɔ trit mɛtabolik sik dɛn. Ɔva di pas sɔm dikɛd ia, di divɛlɔpmɛnt fɔ drɔgs we de tɔch di mɛtabolik sik dɛn dɔn kɔntinyu fɔ go bifo. GLP-1 rεsεptכr agonist dεm εn glukagon rεsεptכr agonist dεn dכn sho sכm tεrapi ifekt dεm we dεn yuz dεm dεn wan, bכt dεn gεt dεn כwn limitεshכn dεm bak. Fɔ fɛn wan mɔ ideal tritmɛnt opshɔn, risach pipul dɛn dɔn pe atɛnshɔn fɔ divɛlɔp drɔgs we kin akt pan bɔku target dɛn wan tɛm, we kin mek dɛn mek Mazdutide. I divεlכpmεnt prכsεs dεn dכn כnda strכng prεklinik stכdi dεm εn mכlti-stej klinik trial dεm, sכmtεm dεn validet in sef εn efficacy.
Mekanism fɔ Akshɔn
(1) Aktivεshכn כf di GLP-1 Risεptor
rεgulεshכn fכ di bכdi glukכs homכstasis: GLP-1 na pεptida כmon we di intestinal L sεl dεm de kכl. afta i aktibכt di GLP-1 rεsεpכta, Mazdutide de rεgεl di bכdi glukכs tru mכltipכl path dεm. i de mek insulin sekreshכn bay pankrεas β sεl dεm, i de εnhans insulin sεnsitiviti, dat de mek di glukכs tek εn yutilizeshכn aksεlεrat, εn i de lכs di blכd glukכs lεvεl. i de inhibit glukagon sekreshכn frכm pankrεas α sεl dεm εn i de ridyus di hεpatik glukכs autput, fכ mεnten di bכdi glukכs stεbiliti mכr.
dilay we di gεstrik εmpti: Mazdutide de aktibכt di GLP-1 rεsεpכta, we de akt pan di gεstrointestinal nεv sεstem fכ slo di gεstrik εmpti. dis de mek di it de rεtεn di bεlε fכ lכng tεm, i de mek di it bכku bכku wan εn i de ridyus di it we yu de it, we de εp fכ kכntrכl di wet.
rεgulεshכn fכ di apitit: afta di GLP-1 rεsεpכta aktibכshכn, signal dεm de transmit to di sεntri nεv sεstem, we de akt pan di haypothalamic fכd sεntr fכ rεgεl di sekreshכn fכ di nyuropεptida dεm we rilet to di apitit, lεk fכ ridyus nyuropεptida Y (NPY) εksprεshכn εn inkrεs di proopiomelanocortin (POMC) εksprεshכn, we de indyuz wan sεns fכ ful εn rεdכks fכ it intake.
(2) Aktivεshכn כf glukagon rεsεpכta dεm
fכ mek di εnεji spεnd: we di glukagכn rεsεpכta de aktibכt bay Mazdutide, i de mek di fεt brok dכn εn fεt asid כksidεshכn, we de mek di εnεji εkspεndεshכn go כp. apat frכm dat, i de upregulate di εksprεshכn fכ uncoupling protein 1 (UCP1), we de protεkt tεmכjεnεsis insay brawn adipos tisu, fכ εnhans di bכdi in enεji mεtabolism εn εp fכ lכs di wet.
rεgulεshכn fכ glukכs mεtabolism: aktibכshכn fכ glukכn rεsεpכta dεm de protεkt hεpatik glycogenolysis εn gluconeogenesis. כl di inflכεns fכ Mazdutide, dis prכmoshכnal ifekt nכ de jכs εlevεt di blכd glukכs lεvεl bכt insted i de achy prεsis bכdi glukכs rεguleshכn tru sinagεstik intarakshכn wit GLP-1 rεsεptכr aktibכshכn ifekt dεm. we di blכd glukכs lεvεl hכy, di haypoglycemic ifekt we GLP-1 rεsεpכta aktibכshכn de mεdiet de prεdominεt; we di blכd glukכs lεvεl dכn lכw, di haypa glycemic ifekt we di glukagon rεsεpכta aktibכshכn de mεdiet de mek di haypoglycemia nכ de.
(3) Sinajɛstik Mɛkanism
Mazdutide de aktibכt כl tu di GLP-1 rεsεpכta dεm εn glukagon rεsεpכta dεm wan tεm. di signal path dεm we dεn tu rεsεpכta dεm ya de aktibכt de wok sinagεstik fכ εksyεrt wan mכr kכmprεhεnsiv εn pawaful mεtabolik rεgεdyushכn ifekt. we i kam pan di wet we yu de lכs, di GLP-1 rεsεpכta aktibכshכn de ridyus di enεji we dεn de tek bay we i de sכpres di apεtit εn delay di gεstrik εmpti, we di glukagon rεsεpכta aktibכshכn de protεkt di εnεji we i de spεnd. di sinagεstik akshכn fכ di tu rεsεpכta dεm mכr ifektiv wan de ajɔst di wet rεdukshכn. we i kam pan di bכdi glukכs rεguleshכn, di ifekt dεm we di tu rεsεpכta aktibכshכn dεm de kכmplit wan wan fכ mεnten di blכd glukכs insay di nכmal rεnj εn fכ avכyd fכ fכlt pasmak.
3. Fisiɔlɔjik Ifɛkt dɛn
(1) Ifɛkt dɛn we pɔsin kin du we i nɔ gɛt bɔku bɔku bɔdi
Klinik pruf: Bɔku klinik trial dɛn dɔn sho se Mazdutide gɛt bɔku ifɛkt dɛn fɔ lɔs yu wet. Insay stεdi dεm we de tכk bכt כvaweit כ fat big pipul dεm insay , 24 wiks fכ Mazdutide tritmεnt (wit maksimal dכz 6 mg) rεsult in avεj weit lכs 6.7%–11.3%, we di plasεbo grup bin εkspiriεns 1.0% wet gεn. Na difrɛn doz grup dɛn, Mazdutide na 4.5 mg ɛn 6 mg sho mɔ pronɔns weit lɔs ifɛkt, wit tritmɛnt difrɛns kɔmpia to plasɛbo we de frɔm -7.7% to -12.3% (P < 0.0001). Insay wan sistamɛtik rivyu ɛn mɛta-analysis we involv 680 patisipan dɛn, Mazdutide sho wan signifyant advantej oba plasɛbo in wet ridɔkshɔn, wit wan min difrɛns (MD) we na -6.22% (95% kɔnfidɛns intaval [CI]: -8.02% to -4.41%).
Figure 2 di εndpכynt dεm fכ di bכdi wet efficacy. a Pasεnt chenj frכm di beslayn in bכdi wet na wik 24. b Pεsεnt chenj frכm di beslayn in bכdi wet ova tεm.
(2) Glycemic Rɛgyuleshɔn Ifɛkt dɛn
Ifɛkt pan di wan dɛn we gɛt tayp 2 dayabitis: Fɔ di wan dɛn we gɛt tayp 2 dayabitis, Mazdutide de ridyus di ɛmoglobin A1c (HbA1c) ɛn di fast blɔd glukɔs lɛvɛl fayn fayn wan. Insay wan rilat randomized, double-blind, placebo-controlled Phase 2 klinik trial, pasɛnt dɛn we gɛt tayp 2 dayabitis we bin gɛt Mazdutide tritmɛnt (na maksimam doz we na 6 mg) fɔ 20 wik, sho wan avɛj chenj na HbA1c we de frɔm -1.41% to -1.67%, we di plasɛbo grup sho chenj we na 0.03%, wit wan statistically signifyant difrɛns kכmpεr to di plasεbo (P < 0.0001). di pesin dεm bin εkspiriεns bak wan big dεkrεshכn pan bכdi wet, wit di avεrej pasεnshכn chenj we sho wan dכz-dipεndεnt rilayshכn, we rich כp to -7.1%.
di advantej dεm we de fכ rεgul di glukכs na di bכdi: Mazdutide nכ de כnli lכs di blכd glukכs lεvεl bכt i de impruv di bכdi glukכs vεryabiliti εn i de ridyus di risk fכ haypoglycemic ivent dεm. We yu kɔmpia am wit tradishɔnal antidayabitik drɔgs, in dual rεsεptכr agonist mεkanism fכ akshכn de ajɔst mכr prεsis εn kכmprεhεnsiv blכd glukכs rεguleshכn, we de impruv di pasεnshכn in kwaliti כf layf εn lכng tεm prכgnosis.
(3) Efεkt pan di kכdivaskyul εn mεtabolik indikεtכr dεm
blכd prεshכn rεgulεshכn: Mazdutide de ridyus כl tu di sistolik εn diastolik blכd prεshכn. Sistεmatik rivyu εn mεta-analysis sho se we yu kכmpεr wit plasεbo, Mazdutide de ridyus sistolik blכd prεshכn bay wan avεj difrεns (MD) we na -7.57 mmHg (95% CI: -11.17 to -3.98 mmHg); fכ diastolik blכd prεshכn rεdukshכn, di MD na bin -2.98 mmHg (95% CI: -5.74 to -0.22 mmHg). dis kin bi fכ Mazdutide in mכltipכl mεkanism dεm, we inklud fכ impruv di vaskulεr εndoteyl fכnshכn, ridyus di pεrifεral vaskulεr rεsistεns, εn fכ rεgεl wata-sכdiכm bεlε.
lipid rεgulεshכn: Mazdutide de rεgεl di lipid profayl dεm fayn fayn wan. I de ridyus di totכl kכlestכl (MD = -16.82%, 95% CI: -24.52 to -9.13%), triglisεrayd (MD = -43.29%, 95% CI: -61.57 to -25.01%), εn lכw-dεnsiti lipoprotein (MD = -17.07%, 95% CI: -25.54 to -8.60%). lεvεl dεm, we i de εksyεrt bak wan sכm rεgεdyushכn ifekt pan hεy-dεnsiti lipoprotein (MD = -7.54%, 95% CI: -11.26 to -3.83%). Dɛn ifɛkt ya kin ɛp fɔ ridyus di risk fɔ gɛt sik na di at ɛn di blɔd ɛn gɛt prɔtɛktiv ifɛkt pan di at ɛn di blɔd sistɛm.
(4) Di tin dɛn we kin apin to pɔsin we gɛt di sik we dɛn kɔl hyperuricemia
Animal εkspεriεns pruf: Insay wan haypayurisεmia (HUA) rat mכdel stכdi, sכbkyutan injεkshכn 0.05 mg/kg εn 0.075 mg/kg Mazdutide (εvri 3 de) sכmtεm rεdכks di sεrum yurik asid (SUA) lεvεl insay rat. We yu kɔmpia am wit di HUA grup, di SUA ɛn sɛrum kriaytinin (SCr) lɛvɛl dɛn bin ridyus bad bad wan na di Maz-MD ɛn Maz-HD grup dɛn, ɛn di urinary protein (U-Pro) lɛvɛl dɛn bin ridyus bak bad bad wan na di Maz-MD grup. Apat fr dat, Mazdutide improv rεnal histopathכlכjik chenj dεm na HUA rat dεm.
Figure 3 a: Pεsεnt chenj frכm di beslayn in bכdi wet ova tεm. b: Prכpכshכn fכ di patisipan dεm we rich di wεyt lכs tכgεt.
Aplikeshɔn Risach
(1) Klinik Trial Prɔgrɛs
Early Clinical Trials: Early Phase 1 klinik trials bin fɔs asɛs di sef, tolɛrabiliti, ɛn di prɛliminari ɛfifikɛshɔn fɔ Mazdutide. Insay wan randomized, placebo-controlled, multiple-dose escalation Phase 1b trial, dɛn gi big pipul dɛn we bin ɔvawej ɔ fat difrɛn doz dɛn fɔ Mazdutide (we go rich 10 mg). Di risal sho se Mazdutide bin wɛl tolɛret insay dis doz rɛnj, wit nɔ siriɔs advays ivin we dɛn ripɔt, ɛn dɛn si signifyant weit lɔs.
Faz 2 klinik trayal: Di Faz 2 klinik trayal validet di efficacy ɛn sef fɔ Mazdutide insay difrɛn pipul dɛn. Insay wan Faz 2 trayal we dɛn bin de tɔch Chaynish pasɛnt dɛn we gɛt tayp 2 dayabitis, Mazdutide bin sho se i gɛt impɔtant ifɛkt fɔ ridyus HbA1c ɛn bɔdi wet, wit sef we kɔmparabl to di plesibo grup. Di kɔmɔn bad bad tin dɛn we kin apin na di bɔdi na bin smɔl to mɔdaret riakshɔn dɛn we kin apin na di bɛlɛ, lɛk dayarɛa ɛn nɔs. Insay wan Faz 2 trayal we dɛn bin de tɔch big pipul dɛn we gɛt bɔku bɔku bɔdi ɔ we fat, 24 wiks we dɛn tek Mazdutide tritmɛnt (we go rich 6 mg) sho se i gɛt gud wet lɔs ɛfifikɛshɔn ɛn sef.
(2) Kɔmpiativ Stɔdi wit Ɔda Drug dɛn
Kכmpεreshכn wit GLP-1 rεsεptכr agonist dεm: we yu kכmpεr wit tradishכnal GLP-1 rεsεptכr agonist dεm, Mazdutide kin gεt mכr signifyant ifekt pan weit lכs εn blכd glukכs rεguleshכn bikoz fכ in dual aktibכshכn fכ GLP-1 rεsεpכta dεm εn glukagon rεsεpכta dεm. insay sכm stכdi dεm, Mazdutide achy bכku weit lכs pas sכm GLP-1 rεsεptכr agonist dεm insay di sem tritmεnt pεriכd εn dεn sho supεriכr stεbiliti in blכd glukכs kכntrכl.
We yu kɔmpia am wit ɔda antidiabetic drɔgs: We yu kɔmpia am wit tradishɔnal ɔral antidiabetic drɔgs, Mazdutide nɔ jɔs de mek di glukɔs na di blɔd go dɔŋ fayn fayn wan bɔt i de gi ɔda bɛnifit dɛn lɛk fɔ lɔs yu wet ɛn fɔ mek yu gɛt bɛtɛ mak dɛn we de mek yu bɔdi wok fayn.
Dɔn
as GLP-1/glucagon dual risεptor agonist, Mazdutide de achy komprεhεnsiv rεguleshכn fכ enεji mεtabolism, bכdi glukכs, blכd prεshכn, εn bכdi lipid dεm bay we i de aktibכt tu imכtant mεtabolik rεgεlεtכri rεsεpכta dεm wan tεm, we de sho mכr kכmprεhεnsiv εn pawaful tεrapi ifekt dεm pas singl rεsεptכr agonist dεm. Mazdutide gɛt impɔtant prɔmis fɔ difrɛn mɛtabolik dizayd dɛm, lɛk fɔ fat, tayp 2 dayabitis, ɛn hyperuricemia.
Sos dɛn we dɛn pul
[1] Zhang B, Cheng Z, Chen J, ɛn ɔda pipul dɛn. Efficacy ɛn Sefty fɔ Mazdutide in Chaynish Patient dɛn wit Tayp 2 Dayabitis: Wan Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial[J]. Dayabitis Keya, 2024,47(1):160-168.DOI:10.2337/dc23-1287.
[2] Nalisa D. L., Kuboia N, Dyab E, ɛn ɔda pipul dɛn. Efficacy ɛn sefty fɔ Mazdutide pan wɛt lɔs bitwin dayabitik ɛn nɔ-dayabitik pasɛnt dɛn: wan sistamɛtik rivyu ɛn mɛta-analysis fɔ randomized kɔntrol trial[J]. Frontiers in Ɛndokrinɔlɔji, 2024,15. https://api.semanticscholar.org/CorpusID:267984513, di wan dɛn we de stɔdi bɔt di Baybul.
[3] Ji L, Jiang H, Cheng Z, ɛn ɔda pipul dɛn. A phase 2 randomized controlled trial of mazdutide in Chaynish ɔvaweit big pipul ɔ big pipul dɛn we gɛt fat[J]. Nature Komyunikeshɔn, 2023,14(1):8289.DOI:10.1038/s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: Wan nyu Glukagon-Lεk Pεptid-1 (GLP-1R) εn Glukagon (GCGR) Risεptor Dual Agonist, Mazdutide (IBI362), Attenuates Hyperuricemia in Hyperuricemic Rats[J]. Dayabitis, 2023. https://api.semanticscholar.org/CorpusID:259452040. Di wan dɛn we de stɔdi bɔt dis sik
[5] Ji L, Gao L, Jiang H, ɛn ɔda pipul dɛn. Sefty ɛn ɛfifikɛshɔn fɔ wan GLP-1 ɛn glukagɔn riseptɔ dual agonist mazdutide (IBI362) 9 mg ɛn 10 mg insay Chaynish big pipul dɛn we gɛt ɔvawej ɔ fat: Wan randomiz, plasɛbo-kɔntrol, mɔltipɛl-asɛnd-dɔz faz 1b trayal[J]. Eklinikalmɛdisin, 2022,54:101691.DOI:10.1016/j.ɛklinm.2022.101691.
Prodak we de fɔ yuz fɔ risach nɔmɔ:
