Isigaba sesi-2 sokuhlolwa komtholampilo kwe-Retatrutide, i-Triple Hormone-Receptor Agonist, yokwelashwa kokukhuluphala.

Ingemuva kanye Nomklamo Wokufunda

I-Retatrutide (LY3437943) iyinoveli yesidakamizwa esisodwa se-peptide esenza kusebenzeama-receptors amathathu ngasikhathi sinyeI-GIP, i-GLP-1, ne-glucagon. Ukuze kuhlolwe ukusebenza kahle nokuphepha kwaso kubantu abanokukhuluphala ngokweqile kodwa abangenaso isifo sikashukela, kwenziwa isigaba 2, okungahleliwe, okungaboni kabili, nokulawulwa kwe-placebo (NCT04881760). Isamba se338 ababambiqhazange-BMI ≥30, noma ≥27 okungenani ene-comorbidity eyodwa ehlobene nesisindo, zahlelwa ngokungahleliwe ukuze zithole i-placebo noma i-retatrutide (1 mg, 4 mg namashejuli amabili we-titration, 8 mg namashejuli amabili we-titration, noma i-12 mg) elawulwa kanye ngesonto ngomjovo ongaphansi kwesikhumba amaviki angu-48. Iisiphetho sokuqalakwakuwushintsho lwephesenti lesisindo somzimba emavikini angu-24, okuneziphetho zesibili ezihlanganisa ukushintsha kwesisindo emavikini angu-48 kanye nemingcele yokuncipha kwesisindo (≥5%, ≥10%, ≥15%).

Imiphumela Ebalulekile

• 24 amasonto: Okungenani-izikwele kusho ushintsho lwephesenti lesisindo somzimba ngokuhlobene nesisekelo

  • Indawo: −1.6%

  • 1 mg: −7.2%

  • 4 mg (kuhlanganisiwe): −12.9%

  • 8 mg (kuhlanganisiwe): −17.3%

  • 12 mg: -17.5%

• 48 amasonto: Ushintsho lwephesenti kwesisindo somzimba kwaba

  • Indawo: −2.1%

  • 1 mg: −8.7%

  • 4 mg (kuhlanganisiwe): −17.1%

  • 8 mg (kuhlanganisiwe): −22.8%

  • 12 mg: -24.2%

Emavikini angama-48, izilinganiso zabahlanganyeli abafinyelela imikhawulo enengqondo yokuncipha kwesisindo bezimangalisa:

• ≥5% ukuncipha kwesisindo: 27% nge-placebo vs. 92–100% emaqenjini asebenzayo

• ≥10%: 9% nge-placebo vs. 73–93% emaqenjini asebenzayo

• ≥15%: 2% nge-placebo vs. 55–83% emaqenjini asebenzayo

Eqenjini le-12 mg, kufika ku-U-26% wabahlanganyeli balahlekelwe ngu-≥30% wesisindo sabo sokuqala, ubukhulu bokuncipha kwesisindo obuqhathaniswa nokuhlinzwa kwe-bariatric.

Ukuphepha
Izehlakalo ezingezinhle ezivame kakhulu kwakuwukuphuma emathunjini (isicanucanu, ukuhlanza, isifo sohudo), ngokuvamile okumaphakathi kuya kokumaphakathi nokuhlobene nomthamo. Imithamo yokuqala ephansi (2 mg titration) inciphise lezi zenzakalo. Ukwenyuka okuhlobene ne-dose ekushayeni kwenhliziyo kwabonwa, kwakhuphuka ngeviki lama-24, bese kwehla. Amazinga okuyekwa asukela ku-6–16% kuwo wonke amaqembu asebenzayo, athi phezulu kune-placebo.

Iziphetho
Kubantu abadala abanokukhuluphala ngaphandle kwesifo sikashukela, i-retatrutide engaphansi kwamaviki angama-48 ikhiqizwaukwehla okukhulu, okuncike kumthamo wesisindo somzimba(kufika ku-24% kusho ukulahlekelwa ngethamo eliphezulu kakhulu), kanye nokuthuthukiswa komaka be-cardiometabolic. Izehlakalo ezimbi zamathumbu zazivamile kodwa zilawuleka nge-titration. Lokhu okutholakele kwesigaba sesi-2 kusikisela ukuthi i-retatrutide ingamela ibhentshimakhi entsha yokwelapha yokukhuluphala, okulinde ukuqinisekiswa ezinhlolweni ezinkulu, zesikhathi eside zesigaba sesi-3.