▎ ʻImi Survodutide
He aha ke kumu noiʻi o Survodutide?
Ka nui o nā maʻi Metabolic:
Me ka wikiwiki o ke ola a me ka hoʻololi ʻana o ke ʻano meaʻai, nā maʻi metabolic e like me ka momona, type 2 diabetes mellitus, a me ka steatohepatitis non-alcoholic (NASH) ua lilo i mau pilikia olakino o ka lehulehu. No ka laʻana, ʻoi aku ka nui o ka maʻi ʻaʻai momona momona (MAFLD) ma mua o 30%, a ua wānana ʻia e 2030, e lilo ka metabolic dysfunction-associated steatohepatitis (MASH) i kumu nui o ka hoʻololi ʻana i ke akepaʻa, e kau ana i kahi kaumaha nui ma ka ʻōnaehana mālama ola.
Nā palena o nā lāʻau lapaʻau e kū nei:
Loaʻa i nā lāʻau GLP-1 kuʻuna i kekahi mau palena i ka mālama ʻana i nā maʻi metabolic. No kekahi poʻe maʻi, ʻaʻole ʻoluʻolu ka hopena o ke kaumaha, a i ʻole e ʻike paha lākou i nā hopena ʻaoʻao o ka ʻōpū. Eia kekahi, ua kaupalena ʻia ko lākou hiki ke hoʻomaikaʻi i ka metabolism momona o ka ate, a hiki ke ulu ka hoʻomanawanui me ka hoʻohana lōʻihi.
Nā mea maikaʻi o Dual Agonists:
Ma ke ʻano he agonist ʻelua o ka glucagon-like peptide-1 receptor (GLP-1R) a me ka glucagon receptor (GCGR), hiki iā Survodutide ke hoʻoponopono i ka metabolism mai nā ʻāpana he nui. Ma o ke ala GLP-1R, hiki iā ia ke hoʻopau i ka ʻai, hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, a hoʻoikaika i ka huna ʻana o ka insulin e hoʻohaʻahaʻa i ka pae koko. Ma o ke ala GCGR, hiki iā ia ke hoʻonui i ka momona momona i loko o ke akepaʻa, hoʻemi i ka hōʻiliʻili momona, a hoʻomaikaʻi pololei i ka fibrosis ate, e hōʻike ana i nā hopena therapeutic maikaʻi i ka momona, ka maʻi diabetes, a me nā maʻi ate i nā hoʻokolohua holoholona.
He aha ke ʻano o ka hana o Survodutide?
1. Palua Receptor Agonism
ʻO Survodutide kahi agonist ʻelua o ka glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R).
GLP-1R Agonism
Ma hope o ka hoʻoulu ʻana o ka mea loaʻa GLP-1, hiki iā ia ke hoʻonui i ka huna ʻana o ka insulin i hilinaʻi ʻia i ka glucose a keʻakeʻa i ka huna ʻana o ka glucagon, a laila e hōʻemi i nā pae glucose koko. Ke hoʻoikaika nei ʻo Survovudutide i ka GLP-1R, hiki iā ia ke hoʻoikaika i ka huna ʻana o ka insulin e ka pancreatic islet β cell a, i ka manawa like, e hoʻemi i ka huna ʻana o ka glucagon e nā pancreatic islet α cell, e loaʻa ai ka hoʻoponopono maikaʻi ʻana o ka glucose koko [1].
Eia kekahi, hiki i ka GLP-1R agonism ke hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū a hoʻonui i ka manaʻo o ka piha, no laila e kōkua ai i ka hōʻemi ʻana i ka ʻai a me ka mālama ʻana i ke kaumaha o ke kino.
GCGR Agonism
Hiki ke hoʻonui i ka hoʻohana ʻana i ka ikehu a hoʻoikaika i ka haki ʻana o ka momona. Hoʻoulu ʻo Survodutide i ka GCGR, hoʻonui i ka pae o ka ikehu o ke kino a hoʻoulu i ka haki ʻana o nā triglycerides i loko o ke kiko adipose i loko o nā momona momona a me ka glycerol, e hāʻawi ana i kahi kumu ikehu no ke kino [1].
2. Nā hopena ma ka Metabolism
Hoʻomaikaʻi i ka Metabolism Glucose
Hoʻemi nui ka Survovudutide i ke kiʻekiʻe o ka hemoglobin glycated (HbA1c). I loko o nā haʻawina hoʻomaʻamaʻa, hōʻike ka poʻe maʻi maʻi diabetes type 2 i mālama ʻia me Survovudutide i kahi emi nui o nā pae HbA1c ma hope o 16 mau pule o ka mālama ʻana. No ka laʻana, i hoʻohālikelike ʻia me ka semaglutide, ʻo ka Survovudutide haʻahaʻa haʻahaʻa (DG2) i loaʻa i kahi hopena like i ka hoʻemi ʻana i ka HbA1c. Ua emi iho ka pae HbA1c i ka hui DG2 e 15.95 mmol / mol (-1.46%), aʻo ka mea ma ka hui semaglutide i emi iho e 16.07 mmol/mol (-1.47%) [1].
Hiki ke hoʻokō ʻia kāna hana ma ka hoʻonui ʻana i ka huna ʻana o ka insulin, kaohi ʻana i ka huna ʻana o ka glucagon, a me ka hoʻomaikaʻi ʻana i ka lawe ʻana a me ka hoʻohana ʻana i ka glucose e nā ʻiʻo peripheral.
Hoʻoponopono i ka Lipid Metabolism
Hiki i ka Survovudutide ke hoʻemi i nā pae lipid koko. Ma ke aʻo ʻana i nā maʻi obese, i hoʻohālikelike ʻia me ka placebo, ua hoʻemi nui ʻo Survodutide i ka pae triglyceride (TG), a ua hoʻemi pū i nā pae o ka lipoprotein haʻahaʻa haʻahaʻa (LDL), kolamu holoʻokoʻa (TC), a me ka lipoprotein cholesterol non-high-density lipoprotein cholesterol (non-HDL-C) i kekahi mau pūʻulu dosis [2].
I ka manawa like, hiki i ka Survodutide ke hōʻemi i ka momona o ka ate. Ma kahi noiʻi o nā maʻi me ka metabolic dysfunction-associated steatohepatitis (MASH), ʻo ka hapa o nā mea maʻi i mālama ʻia me Survovudutide nona ka momona o ka ate i emi iho ma ka liʻiliʻi loa he 30% ʻoi aku ka kiʻekiʻe ma mua o ka hui placebo. No ka laʻana, 63%, 67%, a me 57% o nā mea maʻi i ka Survovudutide 2.4mg, 4.8mg, a me 6.0mg pūʻulu, i hiki i kēia hōʻailona, ʻoiai he 14% wale nō i ka hui placebo [3].
3. Nā hopena ma ka Pūnaehana Cardiovascular
ʻO ka hoʻomaikaʻi ʻana i nā kumu pilikia cardiovascular
Hiki i ka Survovudutide ke hoʻohaʻahaʻa i ke koko. I nā poʻe maʻi obese, i hoʻohālikelike ʻia me ka placebo, ua emi nui ke koko systolic (SBP) a me ke koko diastolic (DBP) ma hope o ka mālama ʻana me Survodutide. I ka hoʻomaʻamaʻa maoli ʻana, hiki i ka Survodutide ke hoʻemi i ka SBP a hiki i 10.2 mmHg a me DBP e 4.8 mmHg, a ua like ka hopena hoʻohaʻahaʻa i ke koko me ka ʻole o ka mea maʻi i ka hypertension ma mua o ka nānā ʻana [2].
Eia kekahi, hiki i ka Survodutide ke hōʻemi i ka pōʻai pūhaka. I nā poʻe maʻi obese, ua emi iho ka ʻāʻī o ka pūhaka o nā maʻi ma nā pūʻulu hoʻopaʻa Survodutide āpau, a ʻo ka hui 4.8mg ka nui o ka hoʻemi ʻana, ʻo ia ka 16.6 cm [2].
Nā hopena ma luna o nā hōʻailona o ka Steatohepatitis non-alcoholic (NASH)
Hiki i ka Survovudutide ke hoʻomaikaʻi i kekahi mau hōʻailona o ka steatohepatitis non-alcoholic (NASH). Ke hōʻike nei nā haʻawina i kēia manawa e hiki ke hana ʻo Survodutide i kahi hana i ka pale ʻana i ka hoʻomohala ʻana o NASH ma o ka hoʻomaikaʻi ʻana i ka momona momona o ka ate a me ke kūlana inflammatory [4].
He aha nā mea hoʻohana o Survodutide?
1. Lapaʻau ʻana i ka maʻi diabetes type 2 a me ka momona
Ma ke ʻano he agonist ʻelua lōʻihi, lawelawe ʻia ʻo Survodutide i hoʻokahi manawa i ka pule a ua hōʻike i nā hopena koʻikoʻi i ka mālama ʻana i ka maʻi diabetes type 2 (T2DM) a me ka momona.
Hoemi i ka Hemoglobin Glycated (HbA1c):
Ua hōʻike ʻia nā hoʻokolohua lapaʻau he nui hiki iā Survodutide ke hōʻemi pono i ka pae HbA1c i nā maʻi. No ka laʻana, ma kahi noiʻi o nā maʻi T2DM, ma hope o 16 mau pule o ka mālama ʻana, ua emi ka pae HbA1c a hiki i 1.7% [4] . He hōʻailona koʻikoʻi ka HbA1c e hōʻike ana i ka mālama ʻana i ka glucose koko no ka wā lōʻihi, a ʻo kona emi ʻana, ʻo ia ka mea ua hoʻomaikaʻi ʻia ka hoʻokele glucose koko o ka mea maʻi.
Pohō kaumaha nui:
No nā poʻe maʻi me ka T2DM a me ka momona, hiki i ka Survodutide ke loaʻa i kahi pohō kaumaha a hiki i ka 14.9% i nā wiki he 46 o ka mālama ʻana [4] . He mea koʻikoʻi kēia no nā poʻe maʻi i pilikia i ka piʻi ʻana o ke kaumaha i hana pinepine ʻia e nā lāʻau antidiabetic kuʻuna. ʻAʻole kōkua wale ka lilo ʻana o ke kaumaha i ka hoʻomaikaʻi ʻana i ke ʻano o ka mea maʻi a me ka maikaʻi o ke ola akā e hōʻemi ana i ka pilikia o nā pilikia e like me nā maʻi cardiovascular.
2. Hoʻomaikaʻi ʻana i nā ʻano pilikia cardiovascular
He hopena maikaʻi hoʻi ka Survodutide i nā kumu pilikia cardiovascular.
Hoemi ke koko:
I loko o kahi hoʻokolohua lapaʻau o nā maʻi obese, i hoʻohālikelike ʻia me ka placebo, hiki iā Survodutide ke hoʻemi i ke koko systolic a hiki i 10.2 mmHg a me ke koko diastolic e 4.8 mmHg [2] . He mea koʻikoʻi ka emi ʻana o ke koko no ka pale ʻana i nā maʻi cardiovascular, ʻoi aku hoʻi no nā poʻe maʻi me ka momona a me ka hypertension.
Hoʻomaikaʻi i nā ʻāpana lipid koko:
Hiki i ka Survodutide ke hoʻemi i ka pae triglyceride (TG) a loaʻa kekahi hopena hoʻomaikaʻi i nā ʻāpana lipid koko e like me ka high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), a me non-high-density lipoprotein cholesterol (non-HDL-C) [2] . No ka laʻana, i ka mālama ʻana i hoʻolālā ʻia, ua emi nui ka TG maʻamau i nā hui Survodutide āpau.
3. Lapaʻau ʻana i ka Steatohepatitis non-alcoholic (NASH)
Hōʻike pū ka Survodutide i ka hiki ke mālama i ka steatohepatitis non-alcoholic (NASH).
ʻO ka hoʻomaikaʻi ʻana i ka Histology Liver:
I loko o ka 48-week, pae 2 hoʻokolohua lapaʻau o nā poʻe maʻi makua me ka MASH (metabolic dysfunction-associated steatohepatitis) a me ka fibrosis ate, ʻoi aku ka maikaʻi o Survodutide ma mua o ka placebo i ka hoʻomaikaʻi ʻana i ka MASH me ka ʻole e hoʻonāukiuki i ka fibrosis ate. Ma keʻano kūikawā, i waena o nā maʻi i mālamaʻia me nāʻano likeʻole o Survodutide, 47% o nā maʻi ma ka hui 2.4mg, 62% o nā maʻi i ka hui 4.8mg, a me 43% o nā maʻi i ka hui 6.0mg i hōʻike i ka holomua ma MASH, aʻo 14% wale nō i ka hui placebo [3].
Hoemi i ka momona o ka ate:
Hiki i ka Survodutide ke hoʻemi i ka momona o ka ate. I loko o ka hoʻokolohua lapaʻau i ʻōlelo ʻia ma luna, 63%, 67%, a me 57% o nā maʻi i mālama ʻia me 2.4mg, 4.8mg, a me 6.0mg doses o Survodutide, kēlā me kēia, ua hōʻemi ʻia ka momona o ka ate ma kahi o 30%, aʻo 14% wale nō i ka hui placebo [3].
Hoʻomaikaʻi i ka fibrosis ate:
Eia kekahi, ua hoʻomaikaʻi ia i ka fibrosis ate i kekahi ʻano. I loko o kēia hoʻokolohua, 34%, 36%, a me 34% o nā maʻi i mālama ʻia me 2.4mg, 4.8mg, a me 6.0mg doses o Survodutide, i hōʻike ʻia i ka hoʻomaikaʻi ʻana i ka fibrosis ate ma kahi o hoʻokahi pae, ʻoiai ʻo 22% i ka hui placebo [3].
4. Ka hopena i nā makemake o ka meaʻai a me ka hoʻomaikaʻi ʻana i ka dyslipidemia
I loko o kahi hiʻohiʻona hamster obese, ʻo Survodutide a me kekahi lāʻau lapaʻau, Semaglutid, hiki ke hoʻoulu i ka pohō kaumaha a hoʻemi i ka index resistance insulin (HOMA-IR), akā loaʻa iā lākou nā hopena like ʻole i nā meaʻai a me ka dyslipidemia.
Ka hopena i ka lawe ʻana i ka meaʻai:
Ua ho'ēmi nuiʻo Semaglutid i ka laweʻana i ka hānai maʻamau a me ka momona momona i ka pule mua o ka mālamaʻana akā ua hoʻi i ka waiwai kumu. I ka manawa like, ua hoʻonui nui i ka lawe ʻana i ka wai maʻamau a hoʻemi i ka lawe ʻana i ka wai momona fructose. I ka hoʻohālikelike ʻana, ʻaʻole i hoʻololi ʻo Survodutide i ka lawe ʻana i ka meaʻai maʻamau a me ka wai maʻamau akā ua hoʻohaʻahaʻa nui i ka lawe ʻana i ka momona momona a me ka wai momona fructose i ka wā mālama 5-wiki [5].
Ka hopena i nā lipid koko:
Hiki i nā Semaglutid a me Survodutide ke hoʻohaʻahaʻa nui i ka nui o ka cholesterol kiʻekiʻe o ka plasma, me ka hoʻemi ʻana o 24% a me 41%. ʻO ka emiʻana o ka nui o ka cholesterol e Semaglutid i alakaʻi i ka 25% emi i ka lipoprotein cholesterol kiʻekiʻe kiʻekiʻe, akā,ʻaʻole i loli ka lipoprotein cholesterol kiʻekiʻe. Ua ʻike ʻia ka hopena hoʻohaʻahaʻa cholesterol o Survodutide i nā ʻāpana lipoprotein āpau, me ka hōʻemi ʻana o 39% i ka lipoprotein cholesterol haʻahaʻa haʻahaʻa [5].
I ka hopena, ma ke ʻano he agonist loaʻa ʻelua, hiki iā Survodutide ke hoʻoponopono i ka metabolism, hoʻohaʻahaʻa i ke koko glucose, hoʻemi i ke kaumaha o ke kino, hoʻomaikaʻi i nā kumu pilikia cardiovascular, a hoʻomaikaʻi i nā hōʻailona o ka steatohepatitis non-alcoholic. Hāʻawi ia i nā manaʻo hou no ka mālama ʻana i nā maʻi pili a he koʻikoʻi nui ia no ka hoʻomaikaʻi ʻana i ke kūlana olakino o nā maʻi.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He kanaka noiʻi ʻo Le Roux C i hui pū me kekahi mau hui. ʻO kēia mau mea he University College Dublin, St Vincents Uni Hosp, Ulster University, Saint Vincent's University Hospital, St Vincents Hosp Grp, KU Leuven, University Hospital Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, University of Gothenburg, Imperial College London, ICL, Univ Dublin, Istituto per la Sintesi Organica e la Fotoreattivita (ISO College), King's College. ʻO ka Hale Hōʻikeʻike ʻo King's College NHS Foundation Trust, Musgrove Park Hospital a me ka Halemai National no Neurology & Neurosurgery.
He ākea kāna mau noiʻi noiʻi - e uhi ana i ka Surgery, Endocrinology & Metabolism, Nutrition & Dietetics, Oncology, a me Biochemistry & Molecular Biology. ʻO kāna hana ma kēia mau wahi e hōʻike ana i kona ʻike nui a me nā haʻawina nui āna i hana ai i ka holomua o ka ʻepekema lapaʻau. Ua helu ʻia ʻo Le Roux C ma ka ʻōlelo kuhikuhi [2].
