Tirzepatid 10mg

▎ Kūlana Tirzepatid

▎ ʻImi ʻo Tirzepatid

He aha ke kumu noiʻi o Tirzepatid?

ʻO Tirzepatid kahi lāʻau polypeptide synthetic. ʻO kāna noiʻi a me ka hoʻomohala ʻana mai ka ʻike hohonu o nā palena o nā agonists receptor GLP-1 i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona i kēlā manawa. ʻOiai ua hōʻike ka GLP-1 receptor agonists i ka hana maikaʻi loa i ka mālama ʻana i ka glucose koko a me ke kaumaha o ke kaumaha, ua ʻike nā kānaka ʻepekema ʻo kā lākou hoʻāla ʻana i ka mea loaʻa GIP he palupalu, kahi e kaupalena ʻia ai ka pono o nā lāʻau lapaʻau i kekahi ʻano. No laila, ua kūpaʻa ka hui noiʻi a me ka hoʻomohala ʻana i ka hoʻomohala ʻana i kahi lāʻau lapaʻau hou e hiki ai ke hoʻoikaika i ka GIPR a me GLP-1R i ka manawa like e hoʻokō ai i ka mana o ka glucose koko a me ka hoʻokele kaumaha ^[1].

I ka wā o ka noiʻi a me ka hoʻomohala ʻana o Tirzepatid, ua hana nā ʻepekema i kahi nui o nā noiʻi kumu a me nā hoʻokolohua lapaʻau. I ka pae noiʻi preclinical, ua hoʻohana ʻia nā hoʻokolohua holoholona e loiloi pono i nā waiwai pharmacodynamic o Tirzepatid. Ua hōʻoia nā hopena i kona hiki ke hoʻomalu i ka glucose koko a me ke kaumaha o ke kaumaha, e kau ana i ke kumu no nā hoʻokolohua lapaʻau ma hope. Ma hope mai, ua komo ʻo Tirzepatid i ka pae hoʻokolohua lapaʻau, me nā pae I, II, a me III. Ua loiloi nui ka Phase I i ka palekana, ka hoʻomanawanui, a me nā waiwai pharmacokinetic o ka lāʻau lapaʻau, a ua hōʻike nā hopena i ka palekana a me ka hoʻomanawanui. Ua ʻimi hou ka Phase II i ka pono a me ka palekana o nā ʻano like ʻole i nā poʻe maʻi me ke ʻano 2 metabolism, e hoʻoholo mua i ka pae o ka hopena kūpono. ʻO ka pae koʻikoʻi III nā hoʻokolohua lapaʻau, e like me ka SURPASS series of study, i komo i ka nui o nā maʻi me ke ʻano 2 metabolism. Ua hōʻike ʻia nā hopena i ʻoi aku ka maikaʻi o Tirzepatid ma mua o nā agonists receptor GLP-1, e like me Semaglutid, i ka hōʻemi ʻana i ka glucose koko a me ke kaumaha, e hāʻawi ana i nā hōʻike ikaika no ka noi kūʻai aku ^[1].

ʻO Tirzepatid kahi polypeptide i haku ʻia me 39 amino acids, a ua hoʻololi ʻia kona ʻano e hoʻomaikaʻi i kona kūpaʻa a me ka pharmacodynamics. ʻO kāna hoʻolālā hoʻolālā kūʻokoʻa e hiki ai iā ia ke hoʻohui i nā hopena o ʻelua incretins, GIP a me GLP-1, i loko o kahi mole hoʻokahi, e hoʻāla ana i nā mea hoʻokipa hormone e pili ana i ka hoʻokele glucose koko ma o ka mīkini ʻelua. ʻO ke kikoʻī, ma ka ʻaoʻao hoʻokahi, hana ia i ka pancreas e hoʻoikaika i ka huna ʻana o ka insulin a kāohi i ka hoʻokuʻu ʻana o ka glucagon e hoʻohaʻahaʻa i ka glucose koko; ma ka ʻaoʻao ʻē aʻe, hana ia ma ke kikowaena o ka ʻōnaehana, hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻonui i ka satiety, hoʻemi i ka makemake a me ka ʻai ʻana i ka meaʻai, a me ka hoʻokō ʻana i ka mālama kaumaha. Hāʻawi kēia mīkini ʻelua iā Tirzepatid i nā pono kūʻokoʻa i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona, e hāʻawi ana i nā mea maʻi i kahi koho lapaʻau piha loa ^[1].

He aha ke ʻano o ka hana a Tirzepatid?

Hoʻohaʻahaʻa ʻo Tirzepatid i ka glucose koko ma o nā ʻano hana he nui:

Hoʻoulu ʻia o nā mea hoʻokipa GLP-1: Hoʻopaʻa ʻo Tirzepatid i nā mea loaʻa GLP-1 ma nā cell beta pancreatic, e hoʻohālike ana i ka hana o ka GLP-1 maoli. ʻO GLP-1 kahi hormone i hana ʻia e ka ʻōpū i mea koʻikoʻi no ka mālama ʻana i ka homeostasis glucose. Hiki iā ia ke hoʻoikaika i ka insulin synthesis, secretion, a me ka ʻike glucose, a hoʻemi i ka huna ʻana o ka glucagon e hoʻoikaika i ka māʻona a hoʻopau i ka ʻai. I nā poʻe maʻi me ke ʻano 2 metabolism, lawa ʻole ka huna ʻana o ka insulin a i ʻole ka hoʻohaʻahaʻa ʻana i ka naʻau kelepona i ka insulin e alakaʻi i ke kiʻekiʻe o ka glucose koko. Hoʻonui ʻo Tirzepatid i ka huna ʻana o ka insulin ma o ka hoʻoulu ʻana i nā mea hoʻokipa GLP-1, e hoʻomaikaʻi ana i ka mana glucose koko. I ka manawa like, hiki i ka hoʻoulu ʻana o nā mea loaʻa GLP-1 ke kāohi i ka hoʻokuʻu ʻana o ka glucagon, e hōʻemi hou i nā kumu o ka glucose koko a me ka hāʻawi ʻana i ka mana glucose koko ^[2].

Hoʻoulu ʻia o nā mea hoʻokipa GIP: Hana ʻo Tirzepatid i nā mea loaʻa GIP, a hiki i kāna hana ke hoʻonui i ka ʻike a me ka huna ʻana o ka insulin. Loaʻa nā mea loaʻa GIP i nā kiko e like me nā pancreatic beta cell. Ma hope o ka hoʻoulu ʻana, ma o ka hoʻololi ʻana i ke ala hōʻailona intracellular, hoʻonui ʻia ka huna ʻana o ka insulin, a hoʻonui ʻia ka pane ʻana o ke kelepona i ka insulin, e hōʻemi pono ana i ka glucose koko ^[2] . ʻO kēia hopena agonist ʻelua ʻelua e ʻoi aku ka maikaʻi o Tirzepatid ma mua o ka GLP-1 receptor agonists i ka hāpai ʻana i ka huna ʻana o ka insulin a me ka pale ʻana i ka hoʻokuʻu glucagon ^[2].

Hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū a me ka hoʻonui ʻana i ka māʻona: Hiki iā Tirzepatid ke hoʻopaneʻe i ka hoʻokuʻu ʻana o ka ʻōpū, hoʻolōʻihi i ka manawa noho o ka meaʻai i loko o ka ʻōpū, hoʻolohi i ka wikiwiki o ka lawe ʻana i nā meaʻai, a pale i ka piʻi ʻana o ka glucose koko postprandial. Hoʻohālikelike ʻia kona hopena i ka hoʻohemo ʻana o ka ʻōpū me ka GLP-1 receptor agonists. I ka manawa like, hana ia i ka ʻōnaehana nerve waena, hoʻonui i ka satiety, hōʻemi i ka makemake a me ka ʻai ʻana i ka meaʻai, kūpono loa ia no ka pilikia obesity i hele pinepine ʻia e nā mea maʻi me ke ʻano 2 metabolism, e kōkua ana i ka hoʻomaikaʻi ʻana i ka insulin resistance a me ke kūlana metabolic holoʻokoʻa ^[2].

Hoʻomaikaʻi i ka Insulin Sensitivity a me Lipid Metabolism: Hiki i ka Tirzepatid ke hoʻonui i ke kiʻekiʻe o ka adiponectin, kahi adipocytokine e pili ana i ka naʻau o ka insulin, e kōkua ana i ka hoʻomaikaʻi ʻana i ka insulin, e hiki ai i nā cell ke lawe pono a hoʻohana i ka glucose, a me ka hōʻemi ʻana i ka glucose koko (Anonymous, 2023). Eia kekahi, hiki iā ia ke hoʻomaikaʻi i ka profile lipid, loaʻa kahi hopena pale i ke olakino cardiovascular. Ua hōʻike ʻia e hiki ke hoʻomaikaʻi i ke koko, hoʻemi i ka LDL cholesterol a me nā triglycerides ^[3].

Puna: PubMed ^[5]

He aha nā haʻawina pili?

ʻO ka maikaʻi ma ka hoʻokele kaumaha i nā maʻi me ka momona a me ke ʻano 2 Metabolism

Ua hōʻoia ka nui o nā noiʻi lapaʻau he hopena koʻikoʻi ko Tirzepatid. Ma ka haʻawina 'SURMOUNT-2', ua mālama ʻia kēia māhele 3, pālua-makapō, randomized, placebo-controlled hoʻokolokolo ma ʻehiku mau ʻāina. ʻO nā mākua (nā makahiki ≥ 18 makahiki) me ka BMI o 27 kg/m² a i ʻole kiʻekiʻe aʻe a me ka HbA₁c o 7 - 10% i kākau inoa ʻia a hāʻawi ʻia e loaʻa i hoʻokahi pule i hoʻokahi pule subcutaneous injection o Tirzepatid (10 mg a i ʻole 15 mg) a i ʻole placebo no 72 mau pule. Ua hōʻike nā hopena i ka pule 72, ʻo ka pakeneka o ka pohō kaumaha ma ka hui Tirzepatid 10 mg a me 15 mg he -12.8% a me -14.7% kēlā me kēia, i hoʻohālikelike ʻia me -3.2% i ka hui placebo. ʻO nā ʻokoʻa i manaʻo ʻia o ka mālama ʻana o Tirzepatid 10 mg a me 15 mg i hoʻohālikelike ʻia me ka placebo he -9.6 pakeneka pākēneka a me -11.6 pākēneka mau helu pakahi, he nui ka helu (p <0.0001). Eia kekahi, ʻoi aku ka nui o nā mea maʻi e loaʻa ana i ka mālama ʻana iā Tirzepatid i hiki i ka paepae o ka 5% a i ʻole ke kaumaha o ke kaumaha (79 - 83% vs 32%) (Garvey WT, 2023). I loko o kēia haʻawina, ʻo ka awelika o ke kaumaha kumu he 100.7 kg, ʻo ka BMI he 36.1 kg/m², a ʻo ka HbA₁c he 8.02%. Ma hope o 72 mau pule o ka mālama ʻana, ʻaʻole wale ʻo Tirzepatid i hoʻemi nui i ke kaumaha o ke kino akā ua loaʻa ka hopena maikaʻi i ka mana glucose koko ^[4].

Hoʻomaikaʻi i ka maʻi maʻi neuropathy

Ua hōʻike ʻia nā haʻawina e hiki i nā GLP1-RA ke hōʻemi i ka hopena o ka dementia i nā mea maʻi me ke ʻano 2 metabolism ma o ka hoʻomaikaʻi ʻana i ka hoʻomanaʻo, ke aʻo ʻana, a me ka lanakila ʻana i ka pilikia cognitive. Ma keʻano he GIP-RA / GLP-1RAʻelua, ma ka laina pūnaewele neuroblastoma (SHSY5Y), uaʻikeʻia ka noiʻi he hopena ko Tirzepatid i nā hōʻailona o ka uluʻana o ka neuronal (CREB a me BDNF), apoptosis (BAX / Bcl2 ratio), kaʻokoʻa (pAkt, MAP2, GAP43, a me AGBL4), a me ka insulin resistance (GLUT41, GLUT41, GLUT41). Hōʻike nā hopena i ka hana a Tirzepatid i ka hoʻoulu ʻana i ke ala pAkt / CREB / BDNF a me nā cascades hōʻailona o lalo a me kāna neuroprotective efficacy, e hōʻike ana e hiki ke pale aku i nā hopena e pili ana i ka hyperglycemia a me ke kū'ē o ka insulin ma ka pae neuronal. No laila, hiki iā Tirzepatid ke hoʻomaikaʻi i ka neurodegeneration i hoʻokumu ʻia e ka hyperglycemia a lanakila i ka pale ʻana o ka insulinal neuronal, e hāʻawi ana i nā ʻike hou i ka hoʻomaikaʻi ʻana i ka neuropathy pili i ka metabolism ^[5].

Ka holomua o ka noiʻi ʻana i ka mālama ʻana i ke ʻano 2 Metabolism

Ma ke ʻano he ʻano hou o ka lāʻau hypoglycemic, ua lilo ʻo Tirzepatid i ʻelua agonist GIP/GLP-1R mua i ʻae ʻia no ka mālama ʻana i ka metabolism ma United States. Ua hōʻoia ka nui o nā hoʻokolohua lapaʻau nui i kona hoʻohaʻahaʻa ʻana i ka glucose koko nui a me nā hopena o ke kaumaha, a hiki iā ia ke pale i ka cardiovascular. Ua wehe ka manaʻo o nā peptides synthetic i nā mea i ʻike ʻole ʻia no Tirzepatid. Ke hoʻomau nei nā hoʻokolohua (NCT04166773) a me nā hōʻike e hōʻike ana he lāʻau hoʻohiki maikaʻi ia i nā kula o ka maʻi ʻaʻai momona ʻole (NAFLD), renal a me neuroprotection ^[6] (Ma Z, 2023).

ʻO ka hopena lōʻihi o Tirzepatid ma ke ola kino

Hiki i ka Tirzepatid ke hoʻemi i ka pilikia o nā maʻi cardiovascular ma o ka hoʻoikaika ʻana i ka pohō kaumaha. Ua nānā ʻia kahi haʻawina i ka hopena o Tirzepatid i ka momona a me nā hanana maʻi cardiovascular i nā pākeke ʻAmelika ^[7] . Ua ʻike ʻia ka noiʻi ʻana i waena o nā poʻe ʻAmelika e pono ai no ka mālama ʻana iā Tirzepatid, ma hope o ka mālama ʻana me 15 mg o Tirzepatid, ua manaʻo ʻia he 70.6% a me 56.7% o nā mākua i nalowale ≥ 15% a me ≥ 20% o ko lākou kaumaha kino, ʻo ia hoʻi he 58.8% ka emi ʻana o ka nui o ka poʻe obese. Ma waena o ka poʻe me ka maʻi ʻole o ka maʻi cardiovascular, ua hoʻemi ʻia ka pilikia o ka maʻi cardiovascular he 10 mau makahiki mai ka 10.1% 'ma mua o ka mālama ʻana' i ka 7.7% 'ma hope o ka mālama ʻana'', me ka hōʻemi maoli ʻana o 2.4% a me ka hōʻemi ʻana i ka pilikia o 23.6%, e pale ana i 2 miliona mau hanana maʻi cardiovascular.

I ka hopena, ʻo Tirzepatid kahi ʻano hou o nā agonist ʻelua o GIP a me GLP-1 receptors, he mea nui loa ia i ka mālama ʻana i ke ʻano 2 metabolism a me ka momona. Hiki iā ia ke hoʻoikaika maikaʻi i ka huna ʻana o ka insulin, kaohi i ka huna ʻana o ka glucagon, hoʻoponopono pololei i ka glucose koko, hōʻemi i ka hopena o nā hoʻopiʻi, hoʻomaikaʻi i ka hana o nā pancreatic beta cell, lohi i ka holomua o ka metabolism, a he hopena cardioprotective. I ka mālama ʻana i ka momona, hiki iā ia ke hōʻemi pono i ka ʻai ʻana i ka meaʻai, hoʻohaʻahaʻa i ka ʻai, hoʻonui i ka satiety, kōkua i nā poʻe maʻi obese e hoʻemi i ke kaumaha, a hoʻemi i ka pilikia o nā pilikia pili i ka momona. Hiki iā ia ke hoʻomaikaʻi i ka insulin resistance a me ka lipid metabolism. Eia kekahi, hōʻike ia i ka hiki i ka mālama ʻana i nā maʻi like ʻole e like me ka steatohepatitis non-alcoholic, sleep apnea syndrome, a me ka pau ʻole o ka naʻau, a hiki i ka manawa like ke hoʻomaikaʻi i nā hōʻailona metabolic he nui, e hāʻawi ana i kahi hoʻolālā lapaʻau piha. Hiki ke hoʻohana ʻia ke ʻano o ka hoʻohana ʻana i hoʻokahi pule i hoʻokahi pule a hiki ke hoʻomaikaʻi i ka mālama ʻana o nā maʻi. Ma ka mālama pono ʻana i ka glucose koko a me ke kaumaha a me ka hōʻemi ʻana i ka pilikia o nā pilikia, hiki iā ia ke hoʻomaikaʻi nui i ke kūlana kino o ka poʻe maʻi, hoʻomaikaʻi i kā lākou hana i kēlā me kēia lā a me ka maikaʻi o ke ola, hoʻonui i ko lākou hilinaʻi i ka mālama ʻana i nā maʻi, hoʻemi i kā lākou kaumaha noʻonoʻo, a hoʻomaikaʻi i kā lākou nohona 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 metabolism mellitus, ka momona, a me kā lākou mau pilikia pili, e manaʻo ana e wehe i nā hoʻolālā therapeutic novel 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 ].

▎ Nā ʻōlelo pili

[1] Nowak M, Nowak W, Grzeszczak W. Tirzepatid - he ʻelua GIP/GLP-1 receptor agonist - he lāʻau antidiabetic hou me ka hana metabolic i ka mālama ʻana i ke ʻano 2 metabolism [J]. Endokrynologia Polska, 2022,73(4):745-755.DOI:10.5603/EP.a2022.0029.

[2] Ka inoa ʻole. ʻO Tirzepatid: ʻO Dual Glucose-Dependent Insulinotropic Polypeptide a me Glucagon-Like Peptide-1 Agonist no ka mālama ʻana i ke ʻano 2 Metabolism Mellitus: Erratum.[J]. American Journal of Therapeutics, 2023,30(3):e311.DOI:10.1097/MJT.0000000000001634.

[3] Forzano I, Varzideh F, Avvisato R, et al. Tirzepatid: He Hōʻano Hou [J]. Ka Nupepa International of Molecular Sciences, 2022,23(23).DOI:10.3390/ijms232314631.

[4] ʻO Garvey WT, Frias JP, Jastreboff AM, a me al. ʻO Tirzepatid i hoʻokahi pule i kēlā me kēia pule no ka mālama ʻana i ka momona i ka poʻe me ke ʻano 2 metabolism (SURMOUNT-2): kahi makapō pālua, randomized, multicentre, placebo-controlled, phase 3 trial [J]. Lancet, 2023,402(10402):613-626.DOI:10.1016/S0140-6736(23)01200-X.

[5] Fontanella RA, Ghosh P, Pesapane A, et al. Kāohi ʻo Tirzepatid i ka neurodegeneration ma o nā ala molekala he nui [J]. Journal of Translational Medicine, 2024,22(1).DOI:10.1186/s12967-024-04927-z.

[6] Ma Z, Jin K, Yue M, et al. Ka holomua o ka noiʻi ʻana ma ka GIP/GLP-1 Receptor Coagonist Tirzepatid, he Hōkū Piʻi i ke ʻano 2 Metabolism [J]. Nūpepa no ka ʻimi noiʻi ʻana, 2023,2023.DOI:10.1155/2023/5891532.

[7] Wong ND, Karthikeyan H, Fan W. ʻO ke kūpono o ka heluna kanaka US a me ka hopena i manaʻo ʻia o ka mālama ʻana iā Tirzepatid i ka maʻi obesity a me nā hanana maʻi cardiovascular [J]. ʻO nā lāʻau lapaʻau cardiovascular a me ka lāʻau lapaʻau, 2024.DOI:10.1007/s10557-024-07583-z.

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.