Eli Lilly's GIP / GLP-1 Dual Receptor Agonist Tirzepatide: Zoo Tshaj Hauv Txo Cov Ntshav Qab Zib Thiab Kev Rog Kom Yuag

Tsis ntev los no Eli Lilly tau tshaj tawm cov txiaj ntsig zoo ntawm kev ntsuas qhov coj ua GIP thiab GLP-1 receptor agonist tirzepatide (LY3298176) hauv kev kho mob ntshav qab zib hom 2 nrog theem III SURPASS-3. Cov ntaub ntawv tau qhia tias tom qab 52 lub lim tiam ntawm kev kho mob, piv nrog insulin deglucon pawg kho mob, glycosylated hemoglobin (A1C) thiab lub cev qhov hnyav ntawm cov neeg mob hauv tirzepatide kev kho mob pab pawg tau qis dua qhov pib.

Raws li kev ntsuam xyuas ntawm kev ua tau zoo, kev txhaj tshuaj ntau tshaj plaws ntawm tirzepatide txo A1C los ntawm 2.37% thiab lub cev hnyav los ntawm 12.9 kg (13.9%). Hauv pawg neeg koob tshuaj no (txhais tau hais tias lub sijhawm mob ntshav qab zib yog 13.3 xyoo), ntau dua ib nrab (62.4%) ntawm cov neeg mob tau A1C qis dua 5.7%. Nov yog ntshav qab zib cov ntshav nyob hauv cov neeg tsis muaj ntshav qab zib. Kev nyab xeeb tag nrho ntawm tirzepatide zoo ib yam li cov lees paub GLP-1 receptor agonist chav kawm ntawm cov tshuaj. Cov kev mob tshwm sim feem ntau tshwm sim yog mob plab hnyuv, uas ua rau kom tsawg zuj zus.

Tirzepatide yog ib zaug ib-lub-piam-piam thaj-insulinotropic polypeptide (GIP, tseem hu ua gastric inhibitory polypeptide) receptor thiab glucagon-zoo li peptide-1 (GLP-1) receptor dual agonist tsim los ntawm Eli Lilly. Cov. Ob qho GIP thiab GLP-1 yog cov tshuaj hormones zais ua haujlwm ntawm lub plab hnyuv, uas tuaj yeem txhawb cov insulin zais cia. Tirzepatide sib xyaw ua ke ntawm ob qhov teebmeem tshuaj insulin mus rau hauv ib lub lwg lej thiab sawv cev ib chav tshiab ntawm cov tshuaj rau kev kho mob ntshav qab zib hom 2.

Nws tsim nyog teev tias tirzepatide yog thawj ob GIP / GLP-1 receptor agonist kom tiav Phase 3 cov kev sim. Thaum Lub Kaum Ob Hlis 2020, Eli Lilly tau tshaj tawm tias Kev Tshawb Fawb III SURPASS-1 kev kho mob monotherapy tau nce mus rau qhov tseem ceeb thiab qhov kawg ntawm qhov kawg: piv rau cov pab pawg placebo, glycosylated hemoglobin (A1C) thiab lub cev qhov hnyav ntawm cov neeg mob hauv tirzepatide kho pawg tau qis dua qis dua lub hauv paus.

SUPERSESS-3 yog 52-lub limtiam randomized, qhib cov ntawv cim sim hauv cov neeg mob ntshav qab zib hom 2 uas tau txais cov tshuaj metformin ruaj khov (nrog lossis tsis muaj SGLT-2 inhibitors) tab sis muaj ntshav qab zib tsis txaus tswj. Qhov ua tau zoo thiab kev nyab xeeb ntawm peb koob (5mg, 10mg thiab 15mg) ntawm tirzepatide thiab titrated insulin degludec. Cov neeg mob uas nkag rau hauv txoj kev tshawb no tsis tau txais kev kho mob insulin-naive, qhov nruab nrab ntawm cov ntshav qab zib ntev yog 8.4 xyoo, hauv paus A1C yog 8.17%, thiab qhov hnyav qhov hnyav yog 94.3 kg.

Hauv txoj kev tshawb fawb no, ob txoj kev kwv yees (kev ntsuas kwv yees [ntsuas kwv yees] thiab kev npaj kho tus qauv [Kho kom zoo-kwv yees kwv yees]) tau siv los sib piv kev sib txawv. Siv tau kwv yees kwv yees hais txog cov nyhuv ua ntej txiav yeeb tshuaj tshawb fawb los yog pib cawm txoj kev kho kom rov qab kho mob loj dua qub. Kev kho kom zoo-kwv yees kwv yees hais txog qhov kev ua tau zoo ntawm kev kho mob ntawm kev mob ntshav siab ceev uas tsis hais seb kev kawm txog tshuaj puas ua raws li lossis kev siv tshuaj cawm los siv.

Cov txiaj ntsig pom tau hais tias txoj kev tshawb fawb tau ua tiav qhov tseem ceeb thiab cov kev ua tiav qib theem kawg siv ob txoj kev kwv yees: tag nrho peb koob tshuaj tiv thaiv tirzepatide muaj kev txo qis zoo dua li cov tshuaj tiv thaiv titrated insulin degludec (qhov nruab nrab 48.8 units / hnub ntawm 52 lub lis piam) Ntshav qab zib ntshav (A1C) thiab qhov hnyav txo cov nyhuv. Ntawm cov neeg mob kho nrog txhua peb koob tshuaj tirzepatide, 92.6% tau A1C< 7%="" (cov="" hom="" phiaj="" kho="" rau="" cov="" neeg="" mob="" ntshav="" qab="" zib="" tau="" pom="" zoo="" los="" ntawm="" american="" diabetes="" association="" [ada]).="" ib="" qho="" ntxiv,="" hais="" txog="" qhov="" xaus="" kev="" ua="" tiav="" theem="" kawg,="" 48.4%="" ntawm="" cov="" neeg="" kho="" mob="" tirzepatide="" muaj="">< 5.7%="" (cov="" neeg="" noj="" qab="" haus="" huv'="" s="" a1c="">

Hauv cov phiaj xwm kev npaj kwv yees, piv nrog suav tshuaj insulin deglu, txhua koob ntawm tirzepatide txo qis A1C thiab lub cev hnyav: (1) A1C txo: -1.85 % (5mg), -2.01 % (10mg), -2.14 % (15mg)), -1.25 % (Insulin de Glut); (2) Lub cev hnyav: -7.0 kg (5 mg), -9.6 kg (10 mg), -11.3 kg (15 mg), +1.9 kg (Insulin de Glut); (3) Qhov kev faib ua feem ntawm cov neeg mob A1C< 7="" %:="" 79.2="" %="" (5mg),="" 81.5="" %="" (10mg),="" 83.5="" %="" (15mg),="" 58.0="" %="" (insulin="" degludec).="" (4)="" qhov="" xwm="" txheej="" ntawm="" cov="" ntshav="" qog="" ntshav="" qab="">< 54="" mg="" dl="" (qib="" 2)="" hauv="" txhua="" pawg="" tirzepatide="" yog="" 1.4="" %="" (5="" mg),="" 1.1="" %="" (10="" mg),="" 2.2="" %="" (15="" mg),="" thiab="" cov="" insulin="" degludec="" pawg="" yog="" 7.3="">

Feem ntau cov kev tsis haum siab hauv cov pab pawg tirzepatide yog cov mob plab, feem ntau me txog rau theem nrab, feem ntau tshwm sim thaum lub sijhawm nce ntxiv, thiab txo nrog qhov nce ntawm koob. Muab piv nrog cov neeg mob hauv cov pab pawg insulin degludec (1.7% [xeev siab], 3.9% [mob plab zom zaws], 1.1% [ntuav]), cov neeg mob tirzepatide (5mg, 10mg, 15mg) pab pawg muaj feem ntau xeev siab (11.5) %, 22.5%), 23.7%), mob plab (15.4%, 16.7%, 15.6%), ntuav (5.9%, 9.4%, 10.0%). Cov kev txiav tawm tsis txaus ntseeg vim muaj cov xwm txheej tsis zoo yog 7.2% (5 mg), 9.7% (10 mg), 10.9% (15 mg), thiab 1.4% (insulin degludec).

Tus thawj coj tshawb fawb txog SURPASS-3 txoj kev tshawb fawb, Dr. Bernhard Ludvik, MD, kws lij choj kws tshuaj hauv Landstrasse Clinic hauv Vienna tau hais tias: "Rau cov neeg mob ntshav qab zib hom 2 uas tau nce mus txog qhov uas lawv tab tom pib kho mob. nrog kev siv tshuaj txhaj, cov txiaj ntsig zoo no tau hais txog lub luag haujlwm ntawm tirzepatide hauv kev txo A1C thiab hnyav. Thoob plaws hauv txoj kev tshawb nrhiav ib xyoos, tirzepatide muab kev txhawb nqa A1C txo qis thiab nce phaus uas muaj qhov tsis tshua muaj tshwm sim ntawm kev mob ntshav qab zib tsawg, uas yog qhov kev txiav txim siab tseem ceeb rau cov neeg mob ntshav qab zib thiab lawv cov chaw kho mob."