Phase 2 Clinical Trial of Retatrutide, Triple Hormone-Receptor Agonist, rau Kev Kho Mob Obesity

Keeb kwm thiab kev kawm tsim

Retatrutide (LY3437943) yog ib hom tshuaj peptide tshiab uas ua raupeb receptors ib txhijGIP, GLP-1, thiab glucagon. Txhawm rau ntsuas nws cov txiaj ntsig thiab kev nyab xeeb hauv cov tib neeg uas muaj rog tab sis tsis muaj ntshav qab zib, theem 2, randomized, ob qhov muag tsis pom kev, kev sim tshuaj placebo tau ua (NCT04881760). Tag nrho ntawm338 cov neeg koomNrog rau BMI ≥30, lossis ≥27 nrog tsawg kawg ib qho kev hnyav hnyav, tau randomized kom tau txais cov placebo los yog retatrutide (1 mg, 4 mg nrog ob lub sij hawm titration, 8 mg nrog ob lub sij hawm titration, los yog 12 mg) noj ib lub lis piam los ntawm kev txhaj tshuaj subcutaneous rau 48 lub lis piam. Covthawj qhov kawgyog qhov feem pua ​​​​ntawm lub cev qhov hnyav ntawm 24 lub lis piam, nrog cov ntsiab lus thib ob suav nrog kev hloov pauv ntawm qhov hnyav ntawm 48 lub lis piam thiab categorical poob qhov hnyav (≥5%, ≥10%, ≥15%).

Cov ntsiab lus tseem ceeb

• 24 lis: Tsawg-squares txhais tau tias feem pua ​​hloov pauv hauv lub cev hnyav piv rau lub hauv paus yog

  • Cov placebo: -1.6%

  • 1 mg: -7.2%

  • 4 mg (ua ke): -12.9%

  • 8 mg (ua ke): -17.3%

  • 12 mg: -17.5%

• 48wej ib: Feem pua ​​ntawm lub cev qhov hnyav tau hloov

  • Cov placebo: -2.1%

  • 1 mg: -8.7%

  • 4 mg (ua ke): -17.1%

  • 8 mg (ua ke): -22.8%

  • 12 mg: -24.2%

Thaum 48 lub lis piam, qhov feem pua ​​​​ntawm cov neeg koom ua tiav cov txiaj ntsig kev noj qab haus huv muaj txiaj ntsig zoo tau txais txiaj ntsig:

• ≥5% poob phaus: 27% nrog cov placebo vs. 92-100% hauv pab pawg nquag

• ≥10%: 9% nrog cov placebo vs. 73-93% hauv pawg active

• ≥15%: 2% nrog cov placebo vs. 55-83% hauv pawg active

Hauv pawg 12 mg, mus txog26% ntawm cov neeg koom poob ≥30% ntawm lawv qhov hnyav, qhov loj ntawm qhov poob phaus piv rau kev phais bariatric.

Kev nyab xeeb
Cov xwm txheej uas tshwm sim feem ntau yog plab hnyuv (xws li xeev siab, ntuav, raws plab), feem ntau me me mus rau nruab nrab thiab cov koob tshuaj. Cov koob tshuaj qis dua (2 mg titration) txo cov xwm txheej no. Kev noj tshuaj ntau ntxiv hauv lub plawv dhia tau pom, nce siab ntawm lub lim tiam 24, tom qab ntawd poob qis. Kev txiav txim siab tsis tu ncua nyob ntawm 6-16% ntawm cov pab pawg nquag, me ntsis siab dua li cov placebo.

Cov lus xaus
Hauv cov neeg laus uas muaj kev rog rog yam tsis muaj ntshav qab zib, txhua lub limtiam subcutaneous retatrutide rau 48 lub lis piam uantau heev, koob tshuaj-raws li kev txo qis hauv lub cev hnyav(txog ~ 24% txhais tau tias poob ntawm koob tshuaj ntau tshaj), nrog rau kev txhim kho hauv cov cim cardiometabolic. Gastrointestinal adverse events tau nquag tab sis tswj tau nrog titration. Cov kev tshawb pom theem 2 no qhia tau hais tias rettrutide tuaj yeem sawv cev rau tus qauv kho tshiab rau kev rog rog, tseem tos kev pom zoo hauv qhov loj dua, mus sij hawm ntev 3 kev sim.