Na Cocer Peptides 
1 mahina aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a maʻi paha. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
1. Hoʻolauna
Ua lilo ka obesity i mea e hopohopo nei i ke olakino lehulehu ma ka honua holoʻokoʻa, me ka hoʻonui nui ʻana i ka pilikia o nā pilikia like ʻole e like me ka maʻi cardiovascular a me ka maʻi diabetes. ʻO ka loaʻa ʻana o nā lāʻau lapaʻau kūpono no ka momona he mea nui loa. ʻO Survodutide, ma ke ʻano he agonist ʻelua e hana ana i ka glucagon receptor (GCGR) a me ka glucagon-like peptide-1 receptor (GLP-1R), hōʻike i ka mana nui i ke kahua o ka mālama ʻana i ka momona.
Kiʻi 1 Nā hopena o ka glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), a me ka glucagon ma nā ʻano mea nui a me nā ʻiʻo.
2. Ka nānā 'ana o Survodutide
2.1 Ka Papa Hoʻomohala
Ke hoʻomau nei ka piʻi ʻana o ke ao holoʻokoʻa o ka momona a me ka type 2 diabetes mellitus (T2DM), a ke alakaʻi pinepine nei nā lāʻau antidiabetic kuʻuna i ka loaʻa ʻana o ke kaumaha, e koi ana i kahi koi wikiwiki no nā lāʻau lapaʻau hou e hiki ke mālama i ka T2DM a me ka momona. Ua hōʻike ʻo GLP-1 receptor agonists (GLP-1 RAs) a me ʻelua GLP-1/GIP receptor agonists i ka maikaʻi o ka pohō kaumaha a me ka hoʻomaikaʻi metabolic, Survodutide (BI 456906) ua puka mai ma ke ʻano he moho hoʻohiki, he agonist ʻelua hana lōʻihi i kēia manawa e hoʻokolokolo ʻia nei.
2.2 Mechanism Target
Aia ka hi'ohi'ona kū'oko'a o Survodutide i kona hiki ke ho'oikaika i ka GCGR a me GLP-1R i ka manawa like. Hoʻoponopono mua ʻo GCGR i nā pae glucose koko, e hoʻoikaika ana i ka glycogenolysis a me ka gluconeogenesis i loko o ke ake ma hope o ka hoʻāla ʻana, a laila e hoʻokiʻekiʻe i nā pae glucose koko. Ma ke ʻano o ka hana a Survodutide, ʻaʻole ia e hoʻokiʻekiʻe wale i nā pae glucose koko akā hoʻoponopono i ka metabolism ikehu ma o ka hana synergistic me GLP-1R. Hoʻolaha nui ʻia ʻo GLP-1R i nā ʻiʻo a me nā ʻāpana he nui, e like me ka pancreas, ka ʻōpū ʻōpū, ka puʻuwai, a me ka lolo. Hoʻoikaika ka GLP-1R i ka huna ʻana o ka insulin, kaohi i ka huna ʻana o ka glucagon, hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻonui i ka satiety, ma laila e hōʻemi ai i ka ʻai ʻana a me ka hoʻohaʻahaʻa ʻana i ke kaumaha o ke kino. Hoʻohana ʻo Survodutide i kahi hopena hoʻoponopono metabolic ʻoi aku ma o ka agonism receptor ʻelua, e kōkua ana i ka mālama ʻana i ka momona.
3. ʻO ke kuleana o Survodutide i ka mālama ʻana i ka momona
3.1 Ka Hooponopono Kaumaha
Ua hōʻike ʻia nā haʻawina lapaʻau he nui he hopena koʻikoʻi ko Survodutide i nā maʻi obese. Ma kahi ho'āʻo hoʻokolohua Phase 2 e huli ana i nā poʻe momona me ka maʻi maʻi ʻole, 387 mau mea komo mai 18 a 75 mau makahiki me ka helu kino kino (BMI) ≥27 kg/m² ua hāʻawi wale ʻia i nā hui ʻelima, e loaʻa ana i kēlā me kēia pule subcutaneous injections o Survodutide (0.6, 2.4, 3.6, a i ʻole 4.8 mg) a i ʻole placebo no 46 mau pule. I ka pau ʻana o nā pule he 46, ua hōʻike nā pūʻulu hōʻemi Survodutide āpau i ka pohō kaumaha, me ka hui 4.8 mg e loaʻa ana i ka hōʻemi kaumaha a hiki i ka 18.7%. Mai ka helu subgroup e ke kāne a me ka BMI, ua hōʻike nā wahine i kahi pohō kaumaha nui aʻe ma hope o ka loaʻa ʻana o 4.8 mg o Survodutide, me ka awelika o ka pohō kaumaha o -17.0%, aʻo nā kāne -11.9%. Ma waena o nā pūʻulu BMI like ʻole, nā mea komo me BMI <30 kg/m² ʻO ka mea i loaʻa iā Survodutide 4.8 mg lapaʻau i ʻike i ka hapa kiʻekiʻe o ka pohō kaumaha, hiki i -19.1%. Hōʻike kēia he hopena hoʻohaʻahaʻa kaumaha ʻo Survodutide i nā poʻe maʻi obese o nā kāne like ʻole a me nā pae BMI, me nā hopena i ʻōlelo ʻia i kekahi mau pūʻulu.
Kiʻi 2 ʻO ka helu hope ma hope o 48 mau pule o ka mālama ʻana.
3.2 Nā hopena i ka hāʻawi ʻana i ka momona o ke kino
Ma waho aʻe o ka nui o ka pohō kaumaha, ua loaʻa i Survodutide nā hopena maikaʻi i ka hāʻawi ʻana i ka momona o ke kino. Hoʻohālikelike ʻia me ka pūʻulu placebo, hōʻike nā pūʻulu dosis Survodutide āpau i ka hōʻemi ʻana i ka pōʻai pūhaka, me ka hui 4.8 mg i loaʻa i ka hōʻemi ʻoi loa o 16.6 cm. ʻO ka hōʻemi ʻana i ka ʻāʻī o ka pūhaka e hōʻike ana i ka emi ʻana o ka momona o ka ʻōpū, pili pono i ka pilikia o ka maʻi cardiovascular. Hōʻike kēia ʻaʻole ʻo Survodutide e hōʻemi wale i ke kaumaha o ke kino akā hoʻomaikaʻi pū kekahi i ka hāʻawi ʻana i ka momona o ke kino ma o ka hōʻemi ʻana i ka momona o ka ʻōpū, a laila e hoʻohaʻahaʻa i ka hopena o nā maʻi cardiovascular pili i ka momona.
3.3 Hoʻomaikaʻi i nā ʻāpana metabolic
ʻAʻole hoʻoponopono wale ʻo Survodutide i ke kaumaha o ke kino akā he hopena maikaʻi nō hoʻi i nā ʻāpana metabolic he nui. Ma ke ʻano o ka lipid metabolism, i ka wā o ka mālama ʻana, ua emi nui nā triglycerides (TG) i nā pūʻulu Survodutide āpau, a ua emi iki ka lipoprotein haʻahaʻa haʻahaʻa (VLDL) i nā pūʻulu hoʻopaʻa Survodutide āpau. Ua emi iho ka LDL ma ka 2.4 a me 3.6 mg mau pūʻulu, aʻo ka nui o ka cholesterol (TC) a me ka non-HDL cholesterol (non-HDL-C) i emi iho ma nā pūʻulu 0.6, 2.4, a me 3.6 mg. Ua paʻa mau ka HDL i ka mālama ʻana. E pili ana i ke koko, i ka mālama maoli ʻana, hiki i ka Survodutide ke hoʻemi i ke koko systolic (SBP) a hiki i 10.2 mmHg a me ke koko diastolic (DBP) e 4.8 mmHg, me nā hopena hoʻohaʻahaʻa koko like ʻole i ʻike ʻia me ka nānā ʻole ʻana i ke kiʻekiʻe ma mua o ka nānā ʻana. ʻO kēia mau hoʻomaikaʻi ʻana i nā ʻāpana metabolic e kōkua i ka hōʻemi ʻana i ka pilikia o ka maʻi cardiovascular i nā maʻi obese, e hōʻike hou ana i nā pono ākea o Survodutide i ka mālama ʻana i ka momona.
3.4 Mechanism of Action
Hoʻohana ʻo Survodutide i kāna mau hopena paona ma ka hoʻāla ʻana iā GCGR a me GLP-1R. Hoʻoikaika ka GLP-1R i ka huna ʻana o ka insulin, hoʻonui i ka naʻau o ka insulin, hoʻopau i ka makemake, a hoʻemi i ka ʻai ʻana i ka meaʻai. Hoʻopaneʻe hoʻi ia i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻolōʻihi i ka manawa e waiho ai ka meaʻai i loko o ka ʻōpū a hoʻonui i ka māʻona. Hoʻokomo ʻia ka GCGR i ka hoʻoponopono metabolic hepatic ma o ka hoʻolaha ʻana i ka momona momona a me ka pale ʻana i ka synthesis momona, a laila e hōʻemi ana i ka hōʻiliʻili momona i ke kino. Hiki i ka Survodutide ke hoʻoikaika i ka metabolism ikehu a me ke kaumaha o ke kino ma o nā ʻano hana like ʻole e like me ka hoʻoponopono ʻana i ka microbiota gut.
4. Hoʻohana i ka Survodutide i ka mālama ʻana i ka momona
4.1 Nā hōʻike noiʻi lāʻau lapaʻau
Ma ke aʻo ʻana i nā poʻe maʻi me ka maʻi diabetes type 2 a me ka momona, ua hōʻike pū ʻo Survodutide i nā hopena hypoglycemic maikaʻi a me ke kaumaha. Ma hope o nā pule he 16 o ka mālama ʻana, ua emi nui nā pae hemoglobin A1c (HbA1c) o ka poʻe maʻi, me ka hōʻemi kiʻekiʻe o 1.7%, a ua emi nui hoʻi ke kaumaha o ke kino, me ka hōʻemi kiʻekiʻe o 14.9%. Ma ke aʻo ʻana o nā poʻe maʻi me ka steatohepatitis pili i ka metabolic dysfunction (MASH) a me ka momona, ʻaʻole i hoʻomaikaʻi wale ʻo Survodutide i nā hōʻailona histological ate akā ua alakaʻi pū ʻia i ka pohō kaumaha o nā maʻi. Ke hōʻoia hou nei kēia mau haʻawina i ka pono o Survodutide i nā heluna like ʻole me nā kūlana pili i ka momona.
4.2 ʻO nā pono hoʻohālikelike ma mua o nā lāʻau lapaʻau ʻē aʻe
Ke hoʻohālikelike ʻia me nā lāʻau hoʻohaʻahaʻa kaumaha maʻamau, hāʻawi ʻo Survodutide i nā pono he nui. Hoʻohana pinepine ʻia nā lāʻau hoʻemi paona kuʻuna i kahi mīkini hoʻokahi, e hopena i ka hopena liʻiliʻi a ʻoi aku ka nui o nā hopena ʻino. Ke hana nei ʻo Survodutide ma o ka agonism receptor ʻelua, e hōʻemi maikaʻi ana i ke kaumaha o ke kino aʻo ka hoʻomaikaʻi ʻana i nā ʻāpana metabolic e like me ke koko glucose, nā pae lipid, a me ke kahe koko, e hāʻawi ana i ka pale ākea a me ka mālama ʻana i nā pilikia pili i ka momona.
Hoʻohālikelike ʻia me nā lāʻau hōʻemi kaumaha ʻē aʻe e like me semaglutide (he agonist receptor GLP-1), i nā hoʻokolohua holoholona, ʻo Survodutide a me semaglutide i hoʻoiho i ke kaumaha kaumaha. Eia nō naʻe, ua hōʻike ʻo Survodutide i nā hopena kūʻokoʻa i nā makemake meaʻai a me nā mea ʻino lipid. Hoʻemi ʻo Semaglutid i ka ʻai ʻana i ka meaʻai i ka hoʻomaka ʻana o ka mālama ʻana akā hoʻi hou i ka pae kumu ma hope, ʻoiai ʻo Survodutide e hoʻemi mau ana i ka lawe ʻana i nā meaʻai momona kiʻekiʻe a me ka wai fructose kiʻekiʻe ma luna o kahi manawa mālama 5-wiki. E pili ana i ka lipid profiles, Semaglutid e hoʻemi nui i ka cholesterol ma ka hoʻohaʻahaʻa ʻana i ka HDL-cholesterol, ʻoiai ʻo Survodutide e hōʻike ana i ka hōʻemi ʻana o ka cholesterol ma nā ʻāpana lipoprotein āpau, me ka LDL-cholesterol. Hōʻike kēia e hāʻawi paha ʻo Survodutide i nā hopena maikaʻi loa i ka hoʻoponopono ʻana i ka ʻai ʻana i ka meaʻai a me nā profile lipid.
5. Ka hopena
ʻO Survodutide, ma ke ʻano he agonist pālua ʻelua o GCGR / GLP-1R, hōʻike i ka pono nui i ka mālama ʻana i ka momona. ʻAʻole ia e hōʻemi wale i ke kaumaha o ke kino a hoʻomaikaʻi i ka hāʻawi ʻana i ka momona o ke kino akā hoʻoponopono pū i nā ʻāpana metabolic he nui e like me ke koko glucose, lipids koko, a me ke koko, e hāʻawi ana i nā pono multifaceted no nā poʻe maʻi me ka momona.
Nā kumu
[1] Yousif A, Hassan E, Mudarres MF, et al. ʻO Survodutide, kahi ākea hou i ka mālama ʻana i ka momona a me ke ʻano diabetes mellitus type 2: He loiloi moʻolelo [J]. Yemen Journal of Medicine, 2024,3:97-101.DOI:10.18231/j.yjom.2024.005.
[2] Le Roux CW, Steen O, Lucas KJ, et al. 6926 Subgroup Analysis by Gender and Body Mass Index (BMI) in People Living With Overweight/Obesity in the Survodutide, a Glucagon/GLP-1 Receptor Dual Agonist, Phase II Trial[J]. Nūpepa o ka Endocrine Society, 2024,8(Supplement_1):bvae133-bvae163.DOI:10.1210/jendso/bvae163.033.
[3] Sanyal AJ, Bedossa P, Fraessdorf M, et al. ʻO kahi hoʻāʻo ʻokoʻa o Survodutide ma ka ʻāpana 2 ma MASH a me Fibrosis.[J]. ʻO ka New England Journal of Medicine, 2024.
[4] Briand F, Augustin R, Bleymehl K, et al. ʻO 7279 Survodutide a me Semaglutid ʻelua e hoʻoulu i ke kaumaha akā e hōʻike i nā hopena like ʻole i ka makemake o ka meaʻai a me ka dyslipidemia i ke koho manuahi ʻo Diet-induced Obese Hamster Model [J]. Nūpepa o ka Endocrine Society, 2024,8(Supplement_1):bvae134-bvae163.DOI:10.1210/jendso/bvae163.034.
[5] ʻO kāna MBU, Rosenstock J, Hoefler J, et al. Nā hopena hopena-pane ma ka HbA1c a me ka hoʻohaʻahaʻa kino o survodutide, kahi ʻelua glucagon/GLP-1 receptor agonist, i hoʻohālikelike ʻia me kahi placebo a me ka inoa open-label semaglutide i nā poʻe me ka maʻi maʻi type 2: kahi hoʻokolohua hoʻokolohua randomized [J]. Diabetologia, 2023,67:470-482.
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