▎ Binciken Survodutide
Menene asalin binciken Survodutide?
Yawaitar Cututtukan Metabolic:
Tare da haɓakar saurin rayuwa da canjin tsarin abinci, cututtuka na rayuwa kamar kiba, nau'in ciwon sukari na 2, da steatohepatitis marasa giya (NASH) sun zama ƙalubalen lafiyar jama'a a duniya. Misali, yawan cututtukan hanta mai hade da metabolism (MAFLD) ya wuce 30%, kuma ana hasashen cewa nan da shekara ta 2030, steatohepatitis dysfunctional dysfunction (MASH) zai zama babban abin da ke haifar da dashen hanta, yana sanya babban nauyi ga tsarin kiwon lafiya.
Iyakancen Magungunan da suke:
Magungunan GLP-1 na gargajiya suna da wasu iyakoki a cikin jiyya na cututtukan rayuwa. Ga wasu marasa lafiya, tasirin asarar nauyi ba shi da gamsarwa, ko kuma suna iya samun sakamako masu illa. Bugu da ƙari, ikon su don inganta ƙwayar hanta mai hanta yana da iyaka, kuma haƙuri na iya haɓaka tare da amfani na dogon lokaci.
Amfanin Dual Agonists:
A matsayin mai dual agonist na mai karɓar glucagon-kamar peptide-1 (GLP-1R) da mai karɓar glucagon (GCGR), Survodutide na iya daidaita metabolism daga ma'auni masu yawa. Ta hanyar GLP-1R, yana iya hana ci, jinkirta zubar da ciki, da haɓaka ƙwayar insulin don rage matakan glucose na jini. Ta hanyar GCGR, yana iya haɓaka iskar oxygen da iskar oxygen a cikin hanta, rage yawan kitse, da kuma inganta fibrosis na hanta kai tsaye, yana nuna kyakkyawan tasirin warkewa akan kiba, ciwon sukari, da cututtukan hanta a cikin gwaje-gwajen dabbobi.
Menene tsarin aikin Survodutide?
1. Dual Receptor Agonism
Survodutide mai dual agonist ne na mai karɓar glucagon (GCGR)/glucagon-kamar peptide-1 mai karɓa (GLP-1R).
GLP-1R Agonism
Bayan kunna mai karɓar GLP-1, yana iya haɓaka haɓakar insulin mai dogaro da glucose kuma yana hana ƙwayar glucagon, ta haka yana rage matakan glucose na jini. Lokacin da Survovudutide ya kunna GLP-1R, yana iya haɓaka siginar insulin ta ƙwayoyin sel na pancreatic islet sel kuma, a lokaci guda, rage ƙwayar glucagon ta sel α na pancreatic, yana samun kyakkyawan tsarin glucose na jini [1]..
Bugu da ƙari, GLP-1R ƙwannafi kuma na iya jinkirta zubar da ciki da kuma ƙara ma'anar cikawa, don haka yana taimakawa wajen rage cin abinci da sarrafa nauyin jiki.
GCGR Agonism
Kunna mai karɓar glucagon na iya ƙara yawan amfani da kuzari da haɓaka rushewar mai. Survodutide yana ƙarfafa GCGR, yana haɓaka matakin makamashi na jiki kuma yana haifar da rushewar triglycerides a cikin adipose nama zuwa fatty acid da glycerol, yana samar da tushen makamashi ga jiki [1].
2. Tasiri akan Metabolism
Inganta Metabolism na Glucose
Survovudutide yana rage matakin glycated haemoglobin (HbA1c). A cikin nazarin asibiti, nau'in ciwon sukari na 2 da aka yi wa maganin Survovudutide ya nuna raguwa sosai a matakan HbA1c bayan makonni 16 na jiyya. Misali, idan aka kwatanta da semaglutide, ƙaramin adadin Survovudutide (DG2) yana da irin wannan tasiri wajen rage HbA1c. Matsayin HbA1c a cikin rukunin DG2 ya ragu da 15.95 mmol/mol (-1.46%), yayin da a cikin rukunin semaglutide ya ragu da 16.07 mmol/mol (-1.47%) [1]..
Ana iya samun hanyar aiwatar da aikin ta ta hanyar haɓaka siginin insulin, hana fitar da glucagon, da haɓaka ɗauka da amfani da glucose ta nama.
Dokokin Lipid Metabolism
Survovudutide na iya rage matakan lipid na jini. A cikin nazarin marasa lafiya masu kiba, idan aka kwatanta da placebo, Survodutide ya rage girman matakin triglyceride (TG), sannan kuma ya rage matakan lipoprotein mai ƙarancin yawa (LDL), jimlar cholesterol (TC), da cholesterol mara nauyi (mara HDL-C) a cikin wasu rukunin kashi [2]..
A lokaci guda, Survodutide kuma na iya rage yawan kitsen hanta. A cikin nazarin marasa lafiya da ke fama da rashin lafiyar da ke da alaƙa da steatohepatitis (MASH), yawan marasa lafiya da aka yi wa maganin su tare da Survovudutide wanda abun ciki na hanta ya ragu da akalla 30% ya fi girma fiye da wannan a cikin rukunin placebo. Misali, 63%, 67%, da 57% na marasa lafiya a cikin Survovudutide 2.4mg, 4.8mg, da 6.0mg, bi da bi, sun kai wannan alamar, yayin da kawai 14% a cikin rukunin placebo [3]..
3. Tasiri akan Tsarin Zuciya
Inganta Abubuwan Haɗarin Zuciya
Survovudutide na iya rage hawan jini. A cikin marasa lafiya masu kiba, idan aka kwatanta da placebo, duka hawan jini na systolic (SBP) da hawan jini na diastolic (DBP) sun ragu sosai bayan jiyya tare da Survodutide. A cikin ainihin magani, Survodutide zai iya rage SBP ta har zuwa 10.2 mmHg da DBP ta 4.8 mmHg, kuma tasirin hawan jini yana kama da ko mai haƙuri yana da hauhawar jini kafin a duba shi [2].
Bugu da ƙari, Survodutide kuma zai iya rage kewayen kugu. A cikin marasa lafiya masu kiba, kewayen kugu na marasa lafiya a cikin duk rukunin kashi na Survodutide ya ragu, kuma rukunin 4.8mg ya sami raguwa mafi girma, wanda shine 16.6 cm [2].
Tasiri kan Alamar Steatohepatitis mara-giya (NASH)
Survovudutide na iya samun ingantaccen tasiri akan wasu alamomin steatohepatitis mara-giya (NASH). Binciken na yanzu ya nuna cewa Survodutide na iya taka rawa wajen hana ci gaban NASH ta hanyar inganta ƙwayar hanta da kuma yanayin kumburi [4].
Menene aikace-aikacen Survodutide?
1. Maganin Nau'in Ciwon Suga Na 2 da Kiba
A matsayin agonist dual mai tsawo, ana gudanar da Survodutide sau ɗaya a mako kuma ya nuna tasiri mai mahimmanci a maganin nau'in ciwon sukari na 2 (T2DM) da kiba.
Rage Haemoglobin Glycated (HbA1c):
Gwaje-gwaje na asibiti da yawa sun nuna cewa Survodutide zai iya rage ƙimar HbA1c yadda ya kamata a cikin marasa lafiya. Misali, a cikin nazarin marasa lafiya na T2DM, bayan makonni 16 na jiyya, matakin HbA1c ya ragu har zuwa 1.7% [4] . HbA1c muhimmiyar alama ce da ke nuna kulawar glucose na jini na dogon lokaci, kuma raguwarta yana nufin cewa an inganta sarrafa glucose na jini na majiyyaci.
Babban Rage Nauyi:
Ga marasa lafiya tare da duka T2DM da kiba, Survodutide zai iya samun asarar nauyi har zuwa 14.9% a lokacin 46 makonni na jiyya [4] . Wannan muhimmin ci gaba ne ga majinyata waɗanda ke cikin damuwa ta hanyar samun nauyi sau da yawa ta hanyar magungunan gargajiya na antidiabetic. Rashin nauyi ba kawai yana taimakawa inganta bayyanar majiyyaci da ingancin rayuwa ba amma yana rage haɗarin rikitarwa kamar cututtukan zuciya.
2. Inganta Abubuwan Haɗarin Zuciya
Survodutide kuma yana da tasiri mai kyau akan abubuwan haɗari na zuciya da jijiyoyin jini.
Rage Hawan Jini:
A cikin gwaji na asibiti na marasa lafiya masu kiba, idan aka kwatanta da placebo, Survodutide zai iya rage karfin jini na systolic har zuwa 10.2 mmHg da diastolic jini ta 4.8 mmHg [2] . Rage hawan jini yana da matukar muhimmanci ga rigakafin cututtukan zuciya, musamman ga masu fama da kiba da hauhawar jini.
Inganta Ma'aunin Lipid na Jini:
Survodutide zai iya rage matakin triglyceride (TG) kuma yana da wani ingantaccen tasiri akan sigogi na lipid na jini kamar babban lipoprotein mai yawa (HDL), ƙananan lipoprotein mai yawa (LDL), jimlar cholesterol (TC), da cholesterol mara nauyi (mara HDL-C) [2] . Misali, a cikin maganin da aka shirya, matsakaicin TG a cikin duk rukunin Survodutide ya ragu sosai.
3. Maganin Steatohepatitis mara-giya (NASH)
Survodutide kuma yana nuna yuwuwar a cikin maganin steatohepatitis mara-giya (NASH).
Inganta Tarihin Hanta:
A cikin 48-mako, lokaci na 2 gwajin gwaji na asibiti na tsofaffi marasa lafiya tare da MASH (magungunan da ke hade da steatohepatitis) da kuma hanta fibrosis, Survodutide ya kasance mafi girma fiye da placebo a inganta MASH ba tare da haɓaka fibrosis na hanta ba. Musamman, a cikin marasa lafiya da aka bi da su tare da nau'o'i daban-daban na Survodutide, 47% na marasa lafiya a cikin rukunin 2.4mg, 62% na marasa lafiya a cikin rukunin 4.8mg, da 43% na marasa lafiya a cikin rukunin 6.0mg sun nuna haɓakawa a cikin MASH, yayin da kawai 14% a cikin rukunin placebo [3]..
Rage Kitsen Hanta:
Survodutide kuma na iya rage kitsen hanta. A cikin gwaji na asibiti da aka ambata a sama, 63%, 67%, da 57% na marasa lafiya da aka bi da su tare da 2.4mg, 4.8mg, da 6.0mg na Survodutide, bi da bi, sun sami raguwa a cikin kitsen hanta na akalla 30%, yayin da kawai 14% a cikin rukunin placebo [3]..
Inganta Hanta Fibrosis:
Bugu da kari, ya inganta hanta fibrosis zuwa wani matsayi. A cikin wannan gwaji, 34%, 36%, da 34% na marasa lafiya da aka bi da su tare da 2.4mg, 4.8mg, da 6.0mg na Survodutide, bi da bi, sun nuna haɓakar fibrosis na hanta na akalla mataki ɗaya, yayin da yake 22% a cikin rukunin placebo [3]..
4. Tasiri kan Zaɓuɓɓukan Abinci da Inganta Ciwon Jiki
A cikin nau'in hamster mai kiba, duka Survodutide da wani magani, Semaglutid, na iya haifar da asarar nauyi da rage ƙimar juriya na insulin (HOMA-IR), amma suna da tasiri daban-daban akan abubuwan da ake so abinci da dyslipidemia.
Tasiri kan Abincin Abinci:
Semaglutid ya rage yawan cin abinci na yau da kullun da abinci mai kitse a cikin makon farko na jiyya amma sai ya koma ƙimar tushe. A lokaci guda, yana haɓaka yawan shan ruwa na yau da kullun kuma yana rage yawan ruwa mai arzikin fructose. Sabanin haka, Survodutide bai canza cin abinci na yau da kullun da ruwa na yau da kullun ba amma ya rage yawan cin abinci mai kitse da ruwa mai wadatar fructose a lokacin jiyya na mako 5 [5].
Tasiri akan Lipids na Jini:
Dukansu Semaglutid da Survodutide na iya rage girman matakin ƙwayar cholesterol cikin jini, tare da raguwar 24% da 41%, bi da bi. Rage yawan adadin ƙwayar cholesterol ta hanyar Semaglutid ya haifar da raguwar 25% a cikin babban matakin lipoprotein cholesterol mai yawa, amma matakin ƙananan ƙwayar cholesterol bai canza ba. An lura da tasirin rage cholesterol na Survodutide a cikin duk abubuwan haɗin lipoprotein, gami da raguwar 39% a cikin ƙananan ƙarancin lipoprotein cholesterol [5].
A ƙarshe, a matsayin agonist mai karɓa na dual, Survodutide na iya daidaita metabolism, rage yawan glucose na jini, rage nauyin jiki, inganta abubuwan haɗari na zuciya da jijiyoyin jini, da kuma inganta alamun steatohepatitis marasa barasa. Yana ba da sababbin ra'ayoyi don maganin cututtukan da ke da alaƙa kuma yana da mahimmanci don inganta lafiyar marasa lafiya.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Le Roux C mai bincike ne mai alaƙa da ƙungiyoyi da yawa. Waɗannan sun haɗa da Kwalejin Jami'ar Dublin, St Vincents Uni Hosp, Jami'ar Ulster, Asibitin Jami'ar Saint Vincent, St Vincent Hosp Grp, KU Leuven, Asibitin Jami'ar Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, Jami'ar Gothenburg, Kwalejin Imperial London, ICL, Univ Dublin, Istituto per e la SintesiCN. Jami'ar, Asibitin Kwalejin King, Asibitin Kwalejin King NHS Foundation Trust, Asibitin Musgrove Park da Asibitin Kasa don Neurology & Neurosurgery.
Abubuwan bincikensa suna da fadi-jeri, rufe tiyata, Endocrinology & Metabolism, Nutrition & Dietetics, Oncology, da Biochemistry & Molecular Biology. Ayyukan da ya yi a cikin waɗannan yankunan yana nuna ƙwarewarsa mai yawa da kuma gagarumar gudunmawar da ya bayar don ci gaban kimiyyar likita. An jera Le Roux C a cikin ambaton ambaton [2].
