Semaglutide mwina ndiye agonist wothandiza kwambiri wa GLP-1.
Pakadali pano, mankhwala ochepetsa thupi omwe amapezeka pamsika amaphatikiza orlistat yochokera ku Roche, liraglutide yochokera ku Novo Nordisk ndi semaglutide.
Wegovy, analogue ya GLP-1 ya Novo Nordisk, adavomerezedwa ndi FDA mu 2017 kuti azichiza matenda amtundu wa 2.Mu June 2021, a FDA adavomereza kuwonetsa kuchepa kwa Wegovy.
Mu 2022, chaka choyamba chathunthu chamalonda pambuyo pa mndandanda wa Wegovy, Wegovy adapeza $ 877 miliyoni pakuchepetsa thupi.
Ndi mndandanda wa semaglutide, kayendetsedwe ka subcutaneous kamodzi pa sabata kwathandizira kwambiri kutsata kwa odwala, ndipo zotsatira zolemetsa ndizodziwikiratu.Kuchepetsa kulemera kwa masabata a 68 ndi 12.5% apamwamba kuposa omwe ali mu placebo (14.9% vs 2.4%), ndipo yakhala chinthu cha nyenyezi pamsika wolemetsa kwa nthawi.
M'gawo loyamba la 2023, Wegovy adapeza ndalama zokwana madola 670 miliyoni aku US, kukwera 225% pachaka.
Chivomerezo cha kuwonetsa kulemera kwa semaglutide makamaka kumachokera ku gawo lachitatu la phunziro lotchedwa STEP.Kafukufuku wa STEP makamaka amayesa chithandizo chamankhwala a subcutaneous jekeseni wa semaglutide 2.4mg kamodzi pa sabata poyerekeza ndi placebo kwa odwala onenepa kwambiri.
Phunziro la STEP linaphatikizapo mayesero angapo, omwe pafupifupi 4,500 odwala olemera kwambiri kapena olemera kwambiri adalembedwa, kuphatikizapo:
STEPI 1 yophunzira (kuthandizidwa ndi moyo wothandizira) poyerekeza ndi chitetezo cha masabata a 68 ndi mphamvu ya jekeseni wa subcutaneous wa semaglutide 2.4mg kamodzi pa sabata ndi placebo mu 1961 obese kapena akuluakulu olemera kwambiri.
Zotsatira zinasonyeza kuti kusintha kwapakati pa kulemera kwa thupi kunali 14.9% mu gulu la semaglutide ndi 2.4% mu gulu la PBO.Poyerekeza ndi PBO, zotsatira za m'mimba za semaglutide ndizofala kwambiri, koma zambiri zimakhala zosakhalitsa ndipo zimatha kutha popanda kuyimitsa nthawi zonse chithandizo chamankhwala kapena kulimbikitsa odwala kuti achoke pa phunzirolo.Kafukufuku wa STEP1 akuwonetsa kuti semaglutide ili ndi zotsatira zabwino zoonda kwa odwala onenepa kwambiri.
STEPI 2 yophunzira (odwala onenepa kwambiri omwe ali ndi matenda amtundu wa 2) adayerekeza chitetezo ndi mphamvu ya jekeseni wa subcutaneous wa semaglutide 2.4 mg kamodzi pa sabata ndi placebo ndi semaglutide 1.0mg mu 1210 onenepa kwambiri kapena akuluakulu onenepa kwa milungu 68.
Zotsatira zinasonyeza kuti chiwerengero cha kulemera kwa thupi chamagulu atatu ochiritsira chinasintha kwambiri, ndi -9.6% pogwiritsa ntchito 2.4 mg ya semaglutide, -7% pogwiritsa ntchito 1.0mg ya semaglutide, ndi -3.4% pogwiritsira ntchito PBO.Kafukufuku wa STEP2 akuwonetsa kuti semaglutide imawonetsanso kuchepa kwa thupi kwa odwala onenepa kwambiri omwe ali ndi matenda amtundu wa 2.
STEP 3 phunziro (adjuvant intensive behaviour therapy) poyerekeza kusiyana kwa masabata a 68 mu chitetezo ndi mphamvu pakati pa jekeseni wa subcutaneous wa semaglutide 2.4 mg kamodzi pa sabata ndi placebo pamodzi ndi mankhwala osokoneza bongo mu 611 obese kapena akuluakulu olemera kwambiri.
M'masabata oyambirira a 8 a phunziroli, maphunziro onse adalandira chakudya chochepa cha calorie cholowa m'malo ndi chithandizo chamankhwala champhamvu pa pulogalamu yonse ya masabata a 68.Otenga nawo mbali akuyeneranso kuchita masewera olimbitsa thupi kwa mphindi 100 sabata iliyonse, ndikuwonjezeka kwa mphindi 25 milungu inayi iliyonse komanso mphindi 200 pa sabata.
Zotsatirazo zinasonyeza kuti kulemera kwa thupi la odwala omwe amathandizidwa ndi semaglutide ndi mankhwala osokoneza bongo kunatsika ndi 16% poyerekeza ndi chiyambi, pamene gulu la placebo linatsika ndi 5.7%.Kuchokera ku deta ya STEP3, tikhoza kuona zotsatira za masewera olimbitsa thupi ndi zakudya pakuchepetsa thupi, koma chochititsa chidwi, kulimbikitsa moyo kumawoneka kuti sikukhala ndi zotsatira zochepa pa kulimbikitsa zotsatira za mankhwala a semaglutide.
(Kuyerekeza kulemera kwapakati pa gulu la Semaglutide ndi gulu la Dulaglutide)
Mankhwalawa amatha kukulitsa kagayidwe ka glucose polimbikitsa maselo a pancreatic β kuti atulutse insulin;Ndipo amalepheretsa ma cell a pancreatic alpha kuti asatulutse glucagon, potero amachepetsa kusala kudya komanso shuga wamagazi a postprandial.
(Kuyerekeza kulemera kwa thupi pakati pa gulu la mankhwala a Semaglutide ndi placebo)
Poyerekeza ndi placebo, Semaglutide imatha kuchepetsa chiopsezo cha mfundo zazikuluzikulu zomaliza (imfa yoyamba yamtima, infatal myocardial infarction, sitiroko yopanda kufa) ndi 26%.Pambuyo pa zaka 2 za chithandizo, Semaglutide ikhoza kuchepetsa kwambiri chiopsezo cha sitiroko chosapha ndi 39%, osapha myocardial infarction ndi 26% ndi imfa ya mtima ndi 2%.Kuonjezera apo, imathanso kuchepetsa kudya kwa chakudya mwa kuchepetsa chilakolako ndi kuchepetsa chimbudzi cha m'mimba, ndipo potsirizira pake kuchepetsa mafuta a thupi, omwe amathandiza kuchepetsa thupi.
Mu phunziro ili, anapeza kuti phentermine-topiramate ndi GLP-1 cholandilira agonist anali anatsimikizira kuti bwino kuwonda-kuonda mankhwala pakati onenepa kwambiri ndi akuluakulu.
