Tirzepatid (GLP-2) 10mg. Di wan dɛn we de wok fɔ di kɔmni

▎ GLP-2 Struktrɔ

▎ GLP-2 Risach

Wetin na di risach bakgrɔn fɔ GLP-2?

GLP-2 na wan sintetik polipεptida dכg. in risεch εn divεlכpmεnt kכmכt frכm dip כndastandin fכ di limitεshכn dεm fכ di GLP-1 rεsεpכta agonist dεm we de naw insay di tritmεnt fכ tayp 2 mεtabolism εn fכ fat da tεm de. pan ɔl we di GLP-1 riseptɔ agonist dɛn dɔn sho fayn fayn wok fɔ kɔntrol di glukɔs na di blɔd ɛn fɔ lɔs di wet, sayɛnsman dɛn dɔn si se dɛn aktiveshɔn fɔ di GIP riseptɔ rili wik, we de stɔp di ɛfifikɛshɔn fɔ di drɔgs to sɔm mak. So, di risach ɛn divɛlɔpmɛnt tim bin dɔn mekɔp dɛn maynd fɔ mek wan nyu drɔg we go ebul fɔ aktiv ɔl tu di GIPR ɛn GLP-1R wan tɛm fɔ ajɔst mɔ kɔmprɛhnsiv ɛn ifektiv blɔd glukɔs kɔntrol ɛn wet mɛnejɛmɛnt ^[1]..

We dɛn bin de du di risach ɛn divɛlɔpmɛnt prɔses fɔ GLP-2, sayɛnsman dɛn bin du bɔku bɔku bɛsik risach ɛn klinik trayal dɛn. In di prεklinik risεch stej, animal εkspεriεns dεm bin yuz fכ evaluate di fכmakodaynamik prכpati dεm fכ GLP-2 gud gud wan. Di rizɔlt dɛn kɔnfyus in pɔtnɛshɛl fɔ kɔntrol di glukɔs na di blɔd ɛn fɔ lɔs di wet, we lay di fawndeshɔn fɔ di klinik trial dɛn we go kam afta dat. afta dat, GLP-2 enta di klinik trial stej, inklud di fεz I, II, εn III. Faz I men wan bin evalyu di sef, tolerabiliti, ɛn famakokinɛtik prɔpati dɛm fɔ di drɔg, ɛn di rizɔlt sho gud sef ɛn tolerabiliti. Faz II fכs εksplכr di efεktiv εn sef fכ difrεn dכz in pasεnshכn wit tayp 2 mεtabolism, fכs dεtermin di ifektiv doz rεnj. Di ki fεz III klinik trayal dεm, lεk di SURPASS siriכs stכdi dεm, involv big nכmba כf pasεnshכn wit tayp 2 mεtabolism. di risalts sho se GLP-2 bin sכmtεm sכmtεm pas di GLP-1 rεsεptכr agonist dεm we bin de, lεk GLP-1, fכ ridyus di blכd glukכs εn wet, we gi strכng pruf fכ di makεt aplikεshכn ^[1]..

GLP-2 na polipεptida we kכmכp fכ 39 amino asid dεm, εn dεn dכn mכdify in strכkchכ fכ impruv in stεbiliti εn fכmakodaynamiks. in yכnik strכkchכral disayn de mek i ebul fכ intagret di ifekt dεm we tu inkrεtin dεm, GIP εn GLP-1, de gi insay wan mכlikul, we de aktibכt di כmon rεsεpכta dεm we de involv fכ kכntrכl di glukכs na di bכdi tru wan tu mεkanism. spεshal wan, na wan say, i de akt pan di pankrias fכ mek insulin sekreshכn εn inhibit glukagon rilis fכ lכs di glukכs na di bכdi; na di כda say, i de wok pan di sεntri nεv sεstem, i de delay di gεstrik εmpti, i de mek yu satisfay bכku, i de rεdכks fכ it εn it, εn i de ajɔst di wet mεnejmεnt. dis tu mεkanism de gi GLP-2 yunik advantej dεm fכ trit di tayp 2 mεtabolism εn fכ fat, we de gi di sik pipul dεm wan mכr kכmprεhεnsiv tritmεnt opshכn ^[1]..

Wetin na di mεkanism fכ akshכn fכ GLP-2?

GLP-2 de lכs di glukכs na di bכdi tru dεn mכltipכl mεkanism dεm ya:

aktibכshכn fכ GLP-1 rεsεpכta dεm: GLP-2 de biεn di GLP-1 rεsεpכta dεm pan pankrεas beta sεl dεm, we de miks di akshכn fכ nεchכral GLP-1. GLP-1 na כmon we di intestin de mek we rili imכtant fכ mek di glukכs homכstasis mεnten. i kin mek insulin sεntez, sekreshכn, εn glukכs sεns, εn rεdכks glukכn sekreshכn fכ mek yu satiet εn sכprεs fכ it. pan di sik pipul dεm we gεt tayp 2 mεtabolism, if insulin sekreshכn nכ de kכmכt כ di sεl dεm we de rεdכks di sεnsitiviti to insulin de mek di bכdi glukכs go כp. GLP-2 de inkrεs insulin sekreshכn bay we i de aktibכt GLP-1 rεsεpכta dεm, we de impruv bכdi glukכs kכntrכl. di sem tεm, di aktibכshכn fכ di GLP-1 rεsεpכta dεm kin inhεbit bak di rilis fכ glukagon, fכ ridyus di sכs dεm fכ di blכd glukכs εn kכntribyut fכ kכntrכl di glukכs na di bכdi ^[2]..

aktibכshכn fכ GIP rεsεpכta dεm: GLP-2 de akt pan GIP rεsεpכta dεm, εn in aktibכshכn kin εnhans insulin sεnsitiviti εn sekreshכn. di GIP risεptor dεm de mεntal wan insay tisu dεm lεk pankrεas beta sεl dεm. afta aktibכt, tru intasεlulyar signal path transdyushכn, insulin sekreshכn de inkrεs, εn di sεl in rεspכns to insulin de εnhans, we de ridyus di blכd glukכs mכr ifektiv wan ^[2] . dis dual risεptor agonist ifekt de mek GLP-2 mכr ifektiv pas singl GLP-1 rεsεptכr agonist dεm fכ protεkt insulin sekreshכn εn inhεbit glukagon rilis ^[2]..

Dilay di gastric Emptying ɛn Increasing Satiety: GLP-2 kin delay gastric emptying, i kin mek di it fɔ de na di bɛlɛ fɔ lɔng tɛm, i kin slo di absɔpshɔn rit fɔ di nyutriɛnt dɛn, ɛn i kin mek di blɔd glukɔs we de afta it nɔ go ɔp shap shap. di ifekt we i gεt pan di gεstrik εmpti de kכmparabl wit di wan we di GLP-1 rεsεpכta agonist dεm de gi. pan di sem tεm, i de akt pan di sεntri nεv sεstem, i de mek di satiety bכku, i de rεdכks fכ it εn di it we yu de it, we de spεshal fכ di fat prכblεm we kin kכmכt wit di sik pipul dεm we gεt tayp 2 mεtabolism, i de εp fכ impruv insulin rεsistεns εn di כvala mεtabolik kכndishכn ^[2]..

Impruv Insulin Sεnsitiviti εn Lipid Dayabitis: GLP-2 kin inkrεs di lεvεl fכ adiponectin, wan adipocytokine we riliyt to insulin sεnsitiviti, we de εp fכ impruv insulin sεnsitiviti, mek di sεl dεm ebul fכ tek εn yuz glukכs mכr ifektiv wan, εn ridyus di glukכs na di bכdi (Anonymous, 2023). apat frכm dat, i kin impruv di lipid profayl bak, we gεt pכtεnshal prכtektiv ifekt pan di kכdivaskyul hεlth. Dɛn dɔn pruv se i ebul fɔ mek blɔd prɛshɔn bɛtɛ, ridyus LDL kɔlɔstrel ɛn triglisɛrɛyd ^[3]..

Sos: PubMed ^{[5] we dɛn pul am.}

Wetin na di stɔdi dɛn we gɛt fɔ du wit dis?

Efficacy pan Weight Management in Patient dɛm wit Ɔbisiti ɛn Tayp 2 Dayabitis

Bɔku klinik stɔdi dɛn dɔn kɔnfyus se GLP-2 gɛt signifyant weit lɔs ifɛkt. Insay di 'SURMOUNT-2' stεdi, dεn bin du dis fεz 3, dכbl-blaynd, randomizεd, plasεbo-kכntrol trial na sεvin kכntri dεm. Adult (we ol ≥ 18 ia) wit BMI we na 27 kg/m² ɔ ay pas dat ɛn HbA2c we na 7 - 10% bin inrɔl ɛn randomly asaynd fɔ gɛt wan tɛm ɛvri wik sabkyutan injɛkshɔn fɔ GLP-2 (10 mg ɔ 15 mg) ɔ plasɛbo fɔ 72 wik. Di risal sho se na wik 72, di pasɛnt we di wet lɔs na di GLP-2 10 mg ɛn 15 mg grup na bin -12.8% ɛn -14.7% rispɛktvɔli, kɔmpia wit -3.2% na di plasɛbo grup. Di ɛstimat tritmɛnt difrɛns fɔ GLP-2 10 mg ɛn 15 mg kɔmpia wit di plesibo na bin -9.6 pasɛnt poɛnt ɛn -11.6 pasɛnt poɛnt rispɛktvɔli, we bin stɛtistikli sifyukɛnt (p < 0.0001). Apat frɔm dat, mɔ pasɛnt dɛn we bin de gɛt GLP-2 tritmɛnt bin rich di trɛshɔld fɔ 5% ɔ mɔ wet lɔs (79 - 83% vs 32%) (Garvey WT, 2023). Insay dis stכdi, di avεrej beslayn wet na bin 100.7 kg, di BMI na bin 36.1 kg/m², εn di HbA0 na bin 8.02%. Afta 72 wiks we dɛn trit am, GLP-2 nɔ bin jɔs ridyus di bɔdi wet bad bad wan bɔt i bin gɛt fayn ifɛkt pan kɔntrol glukɔs na di blɔd ^[4]..

Improvement of Dayabitik Nyuropati

Stɔdi dɔn sho se GLP1-RA kin ridyus di risk fɔ gɛt dis maynia sik pan di sik pipul dɛm we gɛt tayp 2 mɛtabolism bay we i de ɛp fɔ mɛmba, lan, ɛn win di kɔgnitiv impairment. as dual GIP-RA/GLP-1RA, insay di nyuroblastoma sel layn (SHSY5Y), risεch dεn fכnshכn se GLP-2 gεt impak pan mak dεm fכ nyuronal growth (CREB εn BDNF), apoptosis (BAX/Bcl2 rεshכ), difrεns (pAkt, MAP2, GAP43, εn AGBL4), εn insulin rεsistεns (GLUT1, GLUT4, GLUT3, εn SORBS1). di rizulεt dεm εnfaz di rol we GLP-2 de ple fכ aktibכt di pAkt/CREB/BDNF path εn dכwnstrim signal kaskad dεm εn in nyuroprotεktiv efikכs, we sho se i kin kכntrכl di ifekt dεm we de asai wit haypa glycemia εn insulin rεsistεns na di nyuronal lεvεl. fכ dat, GLP-2 kin impruv di nyurodijεnεreshכn we kכz bay haypa glycemia εn i kin כvakom nyuronal insulin rεsistεns, we de gi nyu insayt fכ di impruvmεnt fכ di mεtabolism-rεlatεd nyuropathy ^[5]..

Risach Prɔgrɛs pan di Tritmɛnt fɔ Tayp 2 Dayabitis

as nyu kayn haypoglycemic dכg, GLP-2 dכn bi di fכs dual GIP/GLP-1R agonist we dεn apruv fכ di tritmεnt fכ mεtabolism na Amɛrika. Bɔku big big klinik trial dɛn dɔn kɔnfyus se i de mek di glukɔs we de na di blɔd go dɔŋ ɛn i de mek i nɔ gɛt bɔku bɔku bɔdi, ɛn i gɛt di pawa fɔ protɛkt di at ɛn di blɔd. di kכnsεpt fכ sεntetik pεpti dεm dεn opin plεnti posisibul dεm we dεn nכ no fכ GLP-2. di trayal dεm we de go bifo (NCT04166773) εn pruf dεn sho se na prכmis drog insay di fil dεm fכ nכn-alkohol fεt liva sik (NAFLD), rεnal εn nyuroprotεkshכn ^[6] (Ma Z, 2023).

Lכng tεm Impεkt כf GLP-2 pan Kadivaskyul Hεlth

GLP-2 kin ridyus di risk fɔ gɛt sik dɛn we de ambɔg di at ɛn di blɔd bay we i de mek pɔsin lɔs in wet. Wan stכdi bin egzamin di impak we GLP-2 gεt pan fכ fat εn kכdivaskyul sik ivent dεm na Amɛrikan big pipul dεm ^[7] . Di stכdi fכnshכn se pan Amεriכn big pipul dεm we fit fכ GLP-2 tritmεnt, afta tritmεnt wit 15 mg GLP-2, dεn εstimat 70.6% εn 56.7% pan big pipul dεm lכs ≥ 15% εn ≥ 20% pan dεn bכdi wet rispεktivli, we min se 58.8% ridyus pan di nכmba כf pipul dεm we fat. Na di wan dɛm we nɔ gɛt kadyovaskyuɛl sik, di ɛstimat 10 ia kadiɔvaskyuɛl sik risk dɔn go dɔŋ frɔm 10.1% 'bifo tritmɛnt' to 7.7% 'afta tritmɛnt', wit absɔlɔb risk ridɔkshɔn fɔ 2.4% ɛn rilitiv risk ridɔkshɔn fɔ 23.6%, we mek 2 milyɔn kadiɔvaskyuɛl sik ivin dɛn nɔ apin.

fכ kכnklud, GLP-2 na nyu tכp dual agonist fכ GIP εn GLP-1 rεsεpכta dεm, we gεt big signifyans fכ di tritmεnt fכ tayp 2 mεtabolism εn fכ fat. i kin mek insulin sekreshכn mכr ifektiv, inhibit glukagon sekreshכn, rεgεl di bכdi glukכs prεsis, rεdכks di risk fכ komplikεshכn, impruv di fכnshכn fכ pankrεas beta sεl dεm, delay di prכgreshכn fכ mεtabolism, εn i gεt kכdiprotεktiv ifekt. We dɛn de trit pipul dɛn we fat, i kin rili ridyus di it we dɛn de it, nɔ want fɔ it, i kin mek dɛn satis, ɛp di wan dɛn we fat fɔ lɛf fɔ it bɔku bɔku it dɛn, ɛn i kin mek dɛn nɔ gɛt prɔblɛm dɛn we kin apin we dɛn fat pasmak. I kin mek bak di insulin rɛsistɛns ɛn lipid mɛtabolism bɛtɛ. Apat frɔm dat, i de sho se i kin ebul fɔ trit sik dɛn we gɛt fɔ du wit mɛtabolik abnɔmal tin lɛk stiatohepatitis we nɔ de drink rɔm, slip apnia sindrom, ɛn at pwɛl, ɛn i kin mek bɔku mɛtabolik indikɛtɔ dɛn bɛtɛ wan tɛm, we kin gi mɔ kɔmprɛhnsiv tritmɛnt plan. Di we aw dɛn kin injɛkshɔn wan tɛm insay di wik kin izi fɔ yuz ɛn i kin mek di sikman dɛn fala di tritmɛnt fayn fayn wan. We i kɔntrol di glukɔs ɛn wet na di blɔd fayn fayn wan ɛn ridyus di risk fɔ gɛt prɔblɛm dɛn, i kin rili ɛp fɔ mek di sikman dɛn bɔdi bɛtɛ, i kin mek dɛn ebul fɔ du tin dɛn ɛvride ɛn kwaliti layf, i kin mek dɛn gɛt kɔnfidɛns fɔ kɔntrol di sik, i kin mek dɛn nɔ gɛt bɛtɛ maynd, ɛn i kin mek dɛn ebul fɔ adap to ɔda pipul dɛn.

Bɔt di pɔsin we rayt di buk

Di tin dɛn we wi dɔn tɔk bɔt, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.

Sayɛns Jɔnal Author

Dɔktɔ Wiliam T. Gavi na wan big masta sabi bukman ɛn risachman we gɛt fɔ du wit bɔku bɔku big big institiushɔn dɛn, lɛk di Yunivasiti ɔf Alabama na Bɛmingham, Aston Yunivasiti, ɛn di Bɛmingham Veterans Afɛj Mɛdikal Sɛnta. In akademik bakgrɔn ɛn in wok ɛkspiriɛns span bɔku difrɛn disiplin dɛn insay di mɛdikal ɛn sayɛns fild dɛn. Dɔktɔ Garvey dɔn mek bɔku kɔntribyushɔn to di fil dɛm fɔ ɛndokrinɔlɔji ɛn mɛtabolism, nyutrishɔn ɛn itɛttiks, bayɔkemistri ɛn mɔlikul bayoloji, ɛn bak jenɛral ɛn intanɛnt mɛrɛsin, wit patikyula fɔs pan di kadiovaskular sistɛm ɛn kadiɔlɔji. Bɔku pipul dɛn dɔn no ɛn ɔnɔ in wok, mɔ we dɛn kɔl am Highly Cited Researcher in di Cross-Field kategori fɔ ɔl tu di 2023 ɛn 2024, we sho di big impak ɛn inflɛns we in risach gɛt pan di brayt sayɛns kɔmyuniti.

Dכkta Garvey in risach intres εn εkspεriεns de εksεnd to difrεn aspek dεm fכ mεtabolik sik dεm εn dεn mεnejmεnt. I dɔn de wok tranga wan fɔ stɔdi di mɛtabolism mɛlit, fɔ fat, ɛn di kɔmplikeshɔn dɛn we gɛt fɔ du wit dɛn, we i aim fɔ fɛn nyu tritmɛnt strateji ɛn fɔ mek di pɔsin in autkam bɛtɛ. In wok inkɔmpas besik sayɛns risach, klinik trial, ɛn transleshɔnal stɔdi, we de briŋ di gap bitwin di tin dɛn we dɛn dɔn fɛn na lɛbɔretri ɛn di rial wɔl mɛdikal aplikeshɔn dɛn. Tru in bɔku risach, Dɔkta Garvey dɔn kɔntribyut fɔ ɔndastand mɔ bɔt di ɔndalayn mɛkanism dɛm fɔ mɛtabolik disɔda ɛn i dɔn ɛp fɔ shep klinik gaydlayn ɛn tritmɛnt protɔkɔl dɛm na di fild fɔ ɛndokrinɔlɔji ɛn mɛtabolism. Dɛn rayt Dɔktɔ Wiliam T. Gavi insay di rɛfrɛns fɔ saytayshɔn ^[4 ].

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Nowak M, Nowak W, Grzeszczak W. GLP-2 - wan dual GIP/GLP-1 risεptor agonist - wan nyu antidiabetic drog wit pכtεnshal mεtabolik aktiviti in di tritmεnt fכ tayp 2 mεtabolism[J]. Ɛndokrinɔlɔjia Polska, 2022,73(4):745-755.DOI:10.5603/EP.a2022.0029.

[2] Nɔbɔdi nɔ no in nem. GLP-2: Wan Dual Glukoz-Dipεndεnt Insulinotropik Polipεptida εn Glukagon-Lεk Pεptid-1 Agonist fכ di Mεnejmεnt fכ Tayp 2 Dayabitis Mεllitus: Erratum.[J]. Amɛrikan Jɔnal fɔ Tɛrapi, 2023,30(3):e311.DOI:10.1097/MJT.0000000000001634.

[3] Fɔrzano I, Varzideh F, Avvisato R, ɛn ɔda pipul dɛn. GLP-2: Wan Sistamatik Ɔpdet[J]. Int ɛ rnash ɔ nal J ɔ rnal ɔ f Mɔlikul Sayns, 2022,23(23).DOI:10.3390/ijms232314631.

[4] Garvey WT, Frias JP, Jastreboff A. M., ɛn ɔda pipul dɛn. GLP-2 wan tɛm ɛvri wik fɔ di tritmɛnt fɔ fat pan pipul dɛn we gɛt tayp 2 mɛtabolism (SURMOUNT-2): wan dɛbul-blaynd, randomised, multicentre, placebo-controlled, phase 3 trial[J]. Lancet, 2023,402(10402):613-626.DOI:10.1016/S0140-6736(23)01200-X.

[5] Fontanella R. A., Ghosh P., Pɛsapane A, ɛn ɔda pipul dɛn. GLP-2 de mek nyurodijεnεreshכn tru mכltipכl mכlikul path dεm[J]. J ɔ rnal ov Transleshɔnal Mɛdisin, 2024,22(1).DOI:10.1186/s12967-024-04927-z.

[6] Ma Z, Jin K, Yue M, ɛn ɔda pipul dɛn. Risich Prכgεs pan di GIP/GLP-1 Risεptor Kכagonist GLP-2, wan Rising Star in Tayp 2 Dayabitis[J]. J ɔ rnal ɔ f Dayabitis Risach, 2023,2023.DOI: 10.1155/2023/5891532.

[7] Wong ND, Karthikeyan H, Fan W. US Populεshכn Eligibiliti εn εstimatεd Impεkt כf GLP-2 Tritmεnt pan Obesity Prεvalεns εn Kadivaskyul Disiz Ivent dεm[J]. Kardiovaskular Drug ɛn Tɛrapi, 2024.DOI: 10.1007/s10557-024-07583-z.

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 famasitik, 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.