Phase 2 Clinical Trial of Retatrutide, Triple Hormone-Receptor Agonist, pa Chithandizo cha Kunenepa Kwambiri

Mbiri ndi Kapangidwe ka Phunziro

Retatrutide (LY3437943) ndi mankhwala a single-peptide omwe amayambitsama receptor atatu nthawi imodziGIP, GLP-1, ndi glucagon. Kuti awone momwe zimagwirira ntchito komanso chitetezo chake mwa anthu omwe ali ndi kunenepa kwambiri koma opanda shuga, gawo lachiwiri, losasintha, lopanda khungu, loyang'aniridwa ndi placebo (NCT04881760). Chiwerengero cha338 otenga nawo mbalindi BMI ≥30, kapena ≥27 yokhala ndi vuto limodzi lokhudzana ndi kulemera, adasinthidwa mwachisawawa kuti alandire placebo kapena retatrutide (1 mg, 4 mg ndi ndondomeko ziwiri za titration, 8 mg ndi ndondomeko ziwiri za titration, kapena 12 mg) zomwe zimaperekedwa kamodzi pa sabata ndi jekeseni wa subcutaneous kwa masabata a 48. Thechomaliza choyambirirachinali kusintha kwa kuchuluka kwa kulemera kwa thupi pa masabata a 24, ndi mapeto achiwiri kuphatikizapo kusintha kwa kulemera kwa masabata a 48 ndi chigawo chochepetsera kulemera (≥5%, ≥10%, ≥15%).

Zotsatira zazikulu

• 24 masabata: Ochepa-mabwalo amatanthawuza kuti peresenti ya kusintha kwa kulemera kwa thupi poyerekeza ndi zoyambira zinali

  • Malo: −1.6%

  • 1 mg: -7.2%

  • 4 mg (zophatikiza): -12.9%

  • 8 mg (zophatikiza): -17.3%

  • 12 mg: -17.5%

• 48 masabata: Peresenti kusintha kulemera kwa thupi kunali

  • Malo: −2.1%

  • 1 mg: -8.7%

  • 4 mg (zophatikiza): -17.1%

  • 8 mg (zophatikiza): -22.8%

  • 12 mg: -24.2%

Pamasabata a 48, kuchuluka kwa omwe adatenga nawo gawo pakuchepetsa kuwonda kunali kwakukulu:

• ≥5% kuwonda: 27% ndi placebo vs. 92-100% m'magulu ogwira ntchito

• ≥10%: 9% ndi placebo vs. 73-93% m'magulu ogwira ntchito

• ≥15%: 2% ndi placebo vs. 55-83% m'magulu ogwira ntchito

Mu gulu la 12 mg, mpaka26% ya omwe adatenga nawo gawo adataya ≥30% ya kulemera kwawo koyambira, kukula kwa kuwonda kofanana ndi opaleshoni ya bariatric.

Chitetezo
Choyipa chofala kwambiri chinali cham'mimba (mseru, kusanza, kutsekula m'mimba), nthawi zambiri amakhala ochepa mpaka ochepa komanso okhudzana ndi mlingo. Mlingo woyambira wotsika (2 mg titration) umachepetsa zochitika izi. Kuwonjezeka kwa mlingo wokhudzana ndi kugunda kwa mtima kunawonedwa, kukwera pa sabata 24, ndiyeno kutsika. Miyezo yosiya idachokera ku 6-16% m'magulu onse ogwira ntchito, okwera pang'ono kuposa placebo.

Mapeto
Akuluakulu ndi kunenepa kwambiri popanda shuga, mlungu uliwonse subcutaneous retatrutide kwa masabata 48 opangidwakuchepetsedwa kwakukulu kwa kulemera kwa thupi kumadalira mlingo(mpaka ~ 24% imatanthauza kutayika pa mlingo wapamwamba kwambiri), komanso kusintha kwa zizindikiro za cardiometabolic. Zochitika zoyipa za m'mimba zinali pafupipafupi koma zimatha kuyendetsedwa ndi titration. Zotsatira za gawo la 2 izi zikuwonetsa kuti retatrutide ikhoza kuyimira njira yatsopano yochizira kunenepa kwambiri, podikirira kutsimikiziridwa m'mayesero akulu, anthawi yayitali a 3.