▎ ʻo Tirzepatid ʻImi
He aha ke kumu noiʻi o Tirzepatid?
ʻO ka hoʻomohala ʻana o Tirzepatid, kahi lāʻau polypeptide synthetic, i hoʻomaka ʻia mai ka ʻike ʻana i nā palena o nā agonists receptor GLP-1 i ka mālama ʻana i ka maʻi diabetes type 2 a me ka momona. ʻOiai ʻoi aku ka maikaʻi o ka GLP-1 receptor agonists i ka mālama ʻana i ka glucose koko a me ka pohō kaumaha, ua ʻike nā ʻepekema i ko lākou nāwaliwali nāwaliwali o nā mea loaʻa GIP i kaupalena ʻia nā hopena therapeutic. No laila, ua manaʻo nā hui noiʻi e hoʻomohala i nā lāʻau lapaʻau hou e hiki ai ke hoʻāla i ka GIPR a me GLP-1R no ka hoʻokele glycemic piha a me ka hoʻokele kaumaha [1].
Ua mālama ʻia nā hoʻokolohua preclinical a me nā hoʻokolohua nui i ka wā o ka hoʻomohala ʻana.
Ua loiloi nā haʻawina holoholona preclinical i nā waiwai pharmacodynamic, e hōʻoia ana i kona hiki ke hoʻomalu i ka glycemic a me ka poho kaumaha. ʻO nā hoʻokolohua lapaʻau Phase I i loiloi mua i ka palekana, ka hoʻomanawanui, a me nā pharmacokinetics, e hōʻike ana i ka palekana maikaʻi.
a me ka hoʻomanawanui. Ua ʻimi hou nā hoʻāʻo ʻana o ka Phase II i ka pono a me ka palekana ma nā ʻano like ʻole i nā maʻi maʻi diabetes type 2, me ka hoʻoholo mua ʻana i nā pae hopena kūpono. ʻO nā hoʻokolohua Pivotal Phase III e like me ka SURPASS series, e pili ana i nā cohorts nui o nā maʻi maʻi maʻi type 2, ua hōʻike ʻo Tirzepatid i ʻoi aku ka maikaʻi ma mua o ka GLP-1 receptor agonists i ka hoʻohaʻahaʻa ʻana i ka glucose koko a me ke kaumaha, e hāʻawi ana i nā hōʻike ikaika no nā noi kūʻai ..
Hoʻokumu ʻia he 39 amino acids me nā hoʻololi hoʻololi e hoʻomaikaʻi i ke kūpaʻa a me ka pono, hoʻohui kona ʻano kūʻokoʻa i nā hana a GIP a me GLP-1 i loko o kahi mole hoʻokahi, e hoʻāla ana i nā mea hoʻokipa hormone e pili ana i ka mana glycemic ma o nā mīkini ʻelua.
Ma ka lima hoʻokahi, hana ia ma ka pancreas e hoʻoikaika i ka huna ʻana o ka insulin a keʻakeʻa i ka hoʻokuʻu ʻana o ka glucagon no ka hoʻemi ʻana i ka glucose koko; ma ka ʻaoʻao ʻē aʻe, hana ia ma ke kikowaena o ka ʻōnaehana e hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻonui i ka satiety, a hoʻemi i ka ʻai a me ka ʻai ʻana no ka mālama kaumaha. Hāʻawi kēia ʻano hana ʻelua iā Tirzepatid i nā pono kūʻokoʻa i ka mālama ʻana i ka maʻi maʻi type 2 a me ka momona, e hāʻawi ana i nā mea maʻi i nā koho therapeutic piha loa [1].
He aha ke ʻano o ka hana a Tirzepatid?
Hoʻohaʻahaʻa ʻo Tirzepatid i ka glucose koko ma o nā hana he nui:
Hoʻoulu ʻia o nā mea hoʻokipa GLP-1: Hoʻopaʻa ʻia i nā mea loaʻa GLP-1 ma nā cell pancreatic β, hoʻohālike ia i ka GLP-1 kūlohelohe e hoʻoikaika i ka synthesis insulin, huna, a me ka ʻike glucose i ka wā e hōʻemi ana i ka huna ʻana o ka glucagon e hoʻomaikaʻi i ka satiety a me ka ʻai ʻana. I nā poʻe maʻi maʻi diabetes type 2, ʻo ka hoʻoulu ʻana i nā mea loaʻa GLP-1 e hoʻonui i ka huna ʻana o ka insulin no ka hoʻomaikaʻi ʻana i ka mana glycemic, ʻoiai ke kāohi nei i ka hoʻokuʻu ʻana o ka glucagon e hōʻemi hou i nā kumu glucose koko, e kōkua ana i ka hoʻoponopono glycemic [2].
Hoʻoulu ʻia o nā mea hoʻokipa GIP: Ke hana nei i nā mea loaʻa GIP, hoʻoulu ʻia ka hoʻoulu ʻana i ka ʻike a me ka huna ʻana o ka insulin. Loaʻa nā mea loaʻa GIP i loko o nā ʻiʻo e like me nā pancreatic β cell, a me ka hoʻōla ʻana ma o nā ala hōʻailona intracellular e hoʻonui ai i ka huna ʻana o ka insulin a hoʻomaikaʻi i ka pane ʻana o ke kelepona i ka insulin no ka hōʻemi ʻana i ka glucose koko [2] . ʻO kēia agonism receptor ʻelua e ʻoi aku ka maikaʻi o Tirzepatid i ka hoʻolaha ʻana i ka huna ʻana o ka insulin a me ka pale ʻana i ka hoʻokuʻu ʻana o ka glucagon ma mua o ka GLP-1 receptor agonists [2] .
Hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū a me ka māʻona nui: Hoʻopaneʻe ia i ka hoʻokaʻawale ʻana o ka ʻōpū, hoʻolōʻihi i ka paʻa ʻana o ka meaʻai i loko o ka ʻōpū e hoʻolōʻihi i ka lawe ʻana i nā meaʻai a pale i ka piʻi ʻana o ka glucose koko postprandial. Eia nō naʻe, ʻo ka hana ʻana i ka ʻōnaehana nerve waena e hoʻonui i ka satiety e hōʻemi i ka makemake a me ka ʻai ʻana i ka meaʻai, ʻoi aku ka maikaʻi no ka momona e pili pinepine ʻia me ka maʻi diabetes type 2, e kōkua ana i ka hoʻomaikaʻi ʻana i ka insulin resistance a me ke kūlana metabolic holoʻokoʻa [3].
Hoʻomaikaʻi i ka Insulin Sensitivity a me Lipid Metabolism: Ke hoʻokiʻekiʻe ʻana i nā pae adiponectin - kahi mea momona momona e pili ana i ka ʻike insulin - kōkua i ka hoʻomaikaʻi ʻana i ka ʻike insulin, e hiki ai i nā cell ke lawe pono a hoʻohana i ka glucose no ka hōʻemi ʻana i ke koko [2] (Anonymous, 2023). Hoʻomaikaʻi pū ia i nā profile lipid, me nā hopena palekana i ke olakino cardiovascular, ua hōʻike ʻia e hoʻomaikaʻi i ke koko a hoʻemi i ka LDL cholesterol a me nā triglycerides [3].
He aha nā haʻawina pili?
Hōʻike ʻo Tirzepatid i ka mana koʻikoʻi i ka mālama ʻana i ke kaumaha no nā maʻi maʻi obese a me ke ʻano 2. Ma ka SURMOUNT-2 study, he Phase 3, double-blind, randomized, placebo-controlled trial i hanaʻia ma nā'āinaʻehiku, nā mākua i piha i ≥18 makahiki me BMI ≥27 kg / m² a me HbA1c 7-10% ua hoʻokaʻawale ʻia e loaʻa i kēlā me kēia pule subcutaneous tirzepatide (10 mg a i ʻole 15 mg) a i ʻole placebo no nā pule he 72. Ma ka wiki 72, he −12.8% a me −14.7% ka nui o ka pohō kaumaha ma nā hui tirzepatide 10 mg a me 15 mg me ka −3.2% i loko o ka hui placebo, me nā ʻokoʻa lapaʻau i manaʻo ʻia he −9.6 a me −11.6 pakeneka i hoʻohālikelike ʻia me ka placebo (p <01). Hoʻohui hou, ʻoi aku ka nui o nā maʻi i mālama ʻia i ka tirzepatide i loaʻa i ka ≥5% pohō kaumaha (79-83% vs. 32%) (Garvey WT, 2023). Me ke kaumaha kumu kumu 100.7 kg, BMI 36.1 kg/m², a me HbA1c 8.02%, 72 mau pule o ka mālama ʻana me tirzepatide ʻaʻole wale i hoʻemi nui ʻia ke kaumaha akā ua hoʻomaikaʻi ʻia ka mana glycemic [4] .
I ka hoʻomaikaʻi ʻana i ka neuropathy pili i ka maʻi diabetes, hōʻike ka noiʻi i nā GLP1-RA hiki ke hōʻemi i ka pilikia dementia i nā maʻi maʻi diabetes type 2 ma o ka hoʻomaikaʻi ʻana i ka hoʻomanaʻo, ke aʻo ʻana, a me ka lanakila ʻana i ka hemahema o ka naʻau. Ma keʻano he GIP-RA / GLP-1RAʻelua, ua aʻoʻiaʻo Tirzepatid i nā laina pūnaewele neuroblastoma (SHSY5Y) no kona mau hopena i ka uluʻana o neuronal (CREB a me BDNF), apoptosis (BAX / Bcl2 ratio), kaʻokoʻa (pAkt, MAP2, GAP43, a me AGBL4), a me ka insulin resistance (GLUT1, GLUT3, a me nā kaha insulin. Uaʻikeʻia e hoʻohana i nā hopena neuroprotective ma ka hoʻouluʻana i ke ala pAkt / CREB / BDNF a me nā hōʻailona hōʻailona lalo, e kū'ē i ka hyperglycemia- a me nā hopena pili i ka insulin ma ka pae neuronal. No laila, hiki i ka Tirzepatid ke hoʻomaikaʻi i ka neurodegeneration i hoʻokomo ʻia i ka hyperglycemia a lanakila i ka pale ʻana o ka insulinal neuronal, e hāʻawi ana i nā ʻike hou no ka mālama ʻana i ka neuropathy pili i ka maʻi diabetes [5].
I ka holomua o ka mālama ʻana i ka maʻi diabetes type 2, ua lilo ʻo Tirzepatid, kahi lāʻau lapaʻau hypoglycemic hou, i ʻae ʻia ʻelua GIP/GLP-1R agonist no ka maʻi diabetes ma US Nui nā hoʻokolohua lapaʻau nui e hōʻoia i kāna mau hopena glycemic-lowering a me ke kaumaha, me ka hiki no ka pale cardiovascular. Ua wehe ka manaʻo o nā peptides synthetic i nā mea hiki ʻole i ʻike ʻia no Tirzepatid. Ke hoʻomau nei nā ho'āʻo a me nā hōʻike e hōʻike ana he lāʻau lapaʻau maikaʻi ia no ka maʻi hānai momona ʻole (NAFLD), ka pale ʻana, a me ka neuroprotection [6].
E pili ana i nā hopena lōʻihi i ke olakino cardiovascular, hiki ke hōʻemi ʻo Tirzepatid i ka maʻi cardiovascular (CVD) ma o ka hoʻolaha ʻana i ka pohō kaumaha. Ua ʻike ʻia kahi haʻawina e nānā ana i ka hopena o tirzepatide i ka momona a me nā hanana CVD i ka poʻe mākua US ma waena o ka poʻe i kūpono no ka mālama ʻana i ka tirzepatide, ua manaʻo ʻia ka 15 mg therapy e loaʻa i ka ≥15% a me ≥20% ka pohō kaumaha ma 70.6% a me 56.7% o nā pākeke, kēlā me kēia, e unuhi ana i kahi hōʻemi o ka obes. I nā poʻe me ka CVD ʻole, ua emi mai ka 10-makahiki CVD pilikia mai 10.1% 'pre-treatment' a i 7.7% 'post-treatment,' e hōʻike ana i kahi hōʻemi loa o ka pilikia o 2.4% a me ka hoʻemi ʻana i ka pilikia o 23.6%, hiki ke pale i 2 miliona mau hanana CVD [7].
Ka hopena
I ka hōʻuluʻulu ʻana, ʻo Tirzepatid kahi moʻolelo ʻelua agonist o GIP a me GLP-1 receptors, e paʻa ana i ka mea nui i ka mālama ʻana i ka maʻi diabetes type 2 a me ka momona. Hoʻoikaika maikaʻi ʻo ia i ka huna ʻana o ka insulin, kaohi i ka hoʻokuʻu ʻana o ka glucagon, a hoʻoponopono pololei i ka glucose koko, e hōʻemi ana i nā pilikia hoʻopiʻi ʻoiai e hoʻomaikaʻi ana i ka hana pancreatic β-cell a hoʻopaneʻe i ka piʻi ʻana o ka maʻi diabetes, me nā hopena cardioprotective. I ka mālama ʻana i ka momona, hoʻemi maikaʻi ia i ka ʻai ʻana i ka meaʻai, hoʻopau i ka ʻai, hoʻonui i ka māʻona, kōkua i ka pohō kaumaha, a hoʻohaʻahaʻa i nā pilikia pili i ka momona i ka wā e hoʻomaikaʻi ai i ka pale ʻana o ka insulin a me ka metabolism lipid. Hoʻohui ʻia, hōʻike ia i ka hiki ke mālama i nā maʻi metabolic e like me ka steatohepatitis non-alcoholic, sleep apnea syndrome, a me ka pau ʻole o ka naʻau, e hāʻawi ana i ka mālama piha ʻana ma o ka hoʻomaikaʻi ʻana i nā ʻāpana metabolic he nui. ʻO kāna papa kuhikuhi hoʻokahi pule i kēlā me kēia pule e hoʻonui i ka maʻalahi a me ka hoʻokō hoʻomanawanui. Ma ka hoʻoponopono pono ʻana i ke koko glucose a me ke kaumaha, e hōʻemi ana i nā pilikia complication, a me ka hoʻomaikaʻi nui ʻana i ke kūlana kino, ka hana o kēlā me kēia lā, a me ka maikaʻi o ke ola, hoʻonui ʻo Tirzepatid i ka hilinaʻi o ka poʻe maʻi i ka hoʻokele maʻi, hoʻemi i nā kaumaha psychological, a hoʻonui i ka adaptability.
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
ʻO Kauka William T. Garvey he kanaka naʻauao kaulana a me ka mea noiʻi i hui pū ʻia me nā ʻoihana hanohano he nui, ʻo ia hoʻi ke Kulanui o Alabama ma Birmingham, Aston University, a me ka Birmingham Veterans Affairs Medical Center. ʻO kona ʻano hoʻonaʻauao a me kāna ʻike ʻoihana e pili ana i nā ʻano aʻoaʻo i loko o ka lāʻau lapaʻau a me ka ʻepekema. Ua hāʻawi nui ʻo Kauka Garvey i nā ʻano o ka endocrinology a me ka metabolism, ka meaʻai a me ka meaʻai, biochemistry a me ka molecular biology, a me ka lāʻau lapaʻau maʻamau a i loko, me ka nānā pono ʻana i ka ʻōnaehana cardiovascular a me ka cardiology. Ua ʻike nui ʻia a hoʻohanohano ʻia kāna hana, ʻoiai ua kapa ʻia ʻo ia he Highly Cited Researcher ma ka Cross-Field category no 2023 a me 2024, e hōʻike ana i ka hopena nui a me ka mana o kāna noiʻi ʻana i ke kaiāulu ʻepekema ākea.
Hoʻonui ʻia ko Kauka Garvey makemake noiʻi a me ke akamai i nā ʻano like ʻole o nā maʻi metabolic a me kā lākou hoʻokele. Ua komo ikaika ʻo ia i ke aʻo ʻana i ka maʻi diabetes mellitus, ka momona, a me kā lākou mau pilikia pili, me ka manaʻo e wehe i nā hoʻolālā therapeutic hou a hoʻomaikaʻi i nā hopena maʻi. Hoʻopili ʻia kāna hana i ka noiʻi ʻepekema kumu, nā hoʻokolohua lapaʻau, a me nā noiʻi unuhi, e hoʻopaʻa ana i ka ʻokoʻa ma waena o nā ʻike noiʻi a me nā noi lapaʻau honua maoli. Ma o kāna noiʻi nui, ua hāʻawi ʻo Kauka Garvey i ka ʻike hohonu ʻana i nā ʻano kumu o nā maʻi metabolic a ua kōkua i ke ʻano o nā alakaʻi alakaʻi a me nā protocol lapaʻau ma ke kahua o ka endocrinology a me ka metabolism. Ua helu ʻia ʻo Kauka William T. Garvey ma ka ʻōlelo kuhikuhi [4].
