By Cocer Peptides 
Watanni 1 da suka gabata
DUKKANIN LABARI DA BAYANIN KAYAYYA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Samfuran da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don bincike na in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
1. Gabatarwa
Kiba ya zama abin damuwa game da lafiyar jama'a a duk duniya, yana haɓaka haɗarin rikice-rikice daban-daban kamar cututtukan zuciya da jijiyoyin jini. Nemo ingantattun magungunan maganin kiba yana da matuƙar mahimmanci. Survodutide, a matsayin mai dual agonist da ke aiki akan mai karɓar glucagon (GCGR) da mai karɓar glucagon-kamar peptide-1 (GLP-1R), yana nuna babban yuwuwar a fagen jiyya na kiba.
Hoto 1 Tasirin glucagon-kamar peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), da glucagon akan wasu muhimman gabobin jiki da kyallen takarda.
2. Bayanin Survodutide
2.1 Fagen Ci Gaba
Abubuwan da ke faruwa a duniya na kiba da nau'in ciwon sukari na 2 (T2DM) na ci gaba da hauhawa, kuma magungunan antidiabetic na gargajiya galibi suna haifar da kiba, yana haifar da buƙatar gaggawa na sabbin hanyoyin kwantar da hankali waɗanda za su iya magance T2DM da kiba lokaci guda. GLP-1 agonists masu karɓa (GLP-1 RAs) da dual GLP-1 / GIP agonists masu karɓa sun nuna tasiri a cikin asarar nauyi da haɓakar rayuwa, Survodutide (BI 456906) ya fito a matsayin ɗan takara mai ban sha'awa, mai yin aiki mai tsayi dual agonist a halin yanzu ana gudanar da bincike.
2.2 Makasudin Target
Siffar musamman ta Survodutide tana cikin ikonta na kunna GCGR da GLP-1R lokaci guda. GCGR da farko yana daidaita matakan glucose na jini, yana haɓaka glycogenolysis da gluconeogenesis a cikin hanta yayin kunnawa, ta haka yana haɓaka matakan glucose na jini. A cikin tsarin aikin Survodutide, ba wai kawai yana haɓaka matakan glucose na jini ba amma a maimakon haka yana daidaita metabolism na makamashi ta hanyar aiki tare da GLP-1R. Ana rarraba GLP-1R a cikin kyallen takarda da gabobin da yawa, gami da pancreas, gastrointestinal tract, zuciya, da kwakwalwa. Yin kunna GLP-1R yana haɓaka siginin insulin, yana hana ƙwayar glucagon, jinkirta zubar da ciki, yana ƙaruwa da gamsuwa, ta haka rage cin abinci da rage nauyin jiki. Survodutide yana ba da ƙarin ingantaccen tsarin tsarin rayuwa ta hanyar ƙwannafi mai karɓa na biyu, yana taimakawa wajen kula da kiba.
3. Matsayin Survodutide a cikin Maganin Kiba
3.1 Tasirin Tsarin Nauyi
Yawancin nazarin asibiti sun nuna cewa Survodutide yana da tasiri mai mahimmanci na rage nauyi a cikin marasa lafiya masu kiba. A cikin gwaji na asibiti na Phase 2 wanda ke niyya ga mutane masu kiba ba tare da metabolism ba, mahalarta 387 masu shekaru 18 zuwa 75 tare da ma'aunin jiki (BMI) ≥27 kg / m² An ba da izini ga ƙungiyoyi biyar, suna karɓar allurar subcutaneous mako-mako na Survodutide (0.6, 2.4, 3.6, ko 4.8 mg) ko placebo na makonni 46. A ƙarshen makonni 46, duk ƙungiyoyin kashi na Survodutide sun nuna asarar nauyi, tare da ƙungiyar 4.8 MG suna samun matsakaicin raguwar nauyi har zuwa 18.7%. Daga ƙididdigar rukuni ta hanyar jinsi da BMI, mata sun nuna asarar nauyi bayan sun karbi 4.8 MG na Survodutide, tare da matsakaicin nauyin hasara na -17.0%, yayin da maza ke da -11.9%. Daga cikin ƙungiyoyin BMI daban-daban, mahalarta tare da BMI <30 kg / m² wanda ya karbi maganin Survodutide 4.8 MG ya sami kashi mafi girman asarar nauyi, ya kai -19.1%. Wannan yana nuna cewa Survodutide yana da tasirin rage nauyi a kan marasa lafiya masu kiba na jinsi daban-daban da matakan BMI, tare da ƙarin fa'ida a cikin wasu ƙananan ƙungiyoyi.
Hoto na 2 Farkon Ƙarshen Ƙarshe bayan Makonni 48 na Jiyya na Shirye-shiryen.
3.2 Tasiri akan Rarraba Fat ɗin Jiki
Baya ga asarar nauyi duka, Survodutide kuma yana da tasiri mai amfani akan rarraba mai. Idan aka kwatanta da ƙungiyar placebo, duk ƙungiyoyin kashi na Survodutide sun nuna raguwa a cikin kewayen kugu, tare da ƙungiyar 4.8 MG ta cimma matsakaicin matsakaicin raguwa na 16.6 cm. Rage girman kugu yana nuna raguwar kitsen ciki, wanda ke da alaƙa da haɗarin cututtukan zuciya. Wannan yana nuna cewa Survodutide ba kawai yana rage nauyin jiki ba har ma yana inganta rarraba kitsen jiki ta hanyar rage kitsen ciki, ta yadda zai rage hadarin cututtukan zuciya da ke da alaka da kiba.
3.3 Ingantawa a cikin sigogi na rayuwa
Survodutide ba wai kawai yana daidaita nauyin jiki ba amma kuma yana da tasiri mai kyau akan sigogi na rayuwa da yawa. Dangane da metabolism na lipid metabolism, yayin lokacin jiyya, triglycerides (TG) ya ragu sosai a cikin duk rukunin Survodutide, kuma ƙarancin ƙarancin lipoprotein (VLDL) ya ragu kaɗan a cikin duk rukunin kashi na Survodutide. LDL ya ragu a cikin ƙungiyoyin kashi 2.4 da 3.6 MG, yayin da jimlar cholesterol (TC) da waɗanda ba HDL cholesterol (mara HDL-C) sun ragu a cikin ƙungiyoyin 0.6, 2.4, da 3.6 MG. HDL ya kasance da kwanciyar hankali a duk lokacin jiyya. Game da cutar hawan jini, a cikin ainihin magani, Survodutide zai iya rage karfin jini na systolic (SBP) har zuwa 10.2 mmHg da diastolic blood pressure (DBP) ta 4.8 mmHg, tare da irin wannan tasirin hawan jini da aka lura ba tare da la'akari da ko hawan jini ya kasance ba kafin nunawa. Waɗannan haɓakawa a cikin sigogi na rayuwa suna taimakawa rage haɗarin cututtukan zuciya da jijiyoyin jini a cikin marasa lafiya masu kiba, suna ƙara nuna fa'idodin Survodutide a cikin kula da kiba.
3.4 Tsarin Aiki
Survodutide yana aiwatar da tasirinsa na asarar nauyi ta kunna GCGR da GLP-1R. Kunna GLP-1R yana haɓaka ƙwayar insulin, yana haɓaka haɓakar insulin, yana hana ci, da rage cin abinci. Har ila yau, yana jinkirta zubar da ciki, yana tsawaita lokacin da abinci ya kasance a cikin ciki da kuma kara yawan jin dadi. Kunna GCGR yana shiga cikin ka'idojin metabolism na hanta ta hanyar haɓaka iskar oxygen da kuma hana haɓakar mai, ta haka ne ke rage tarin kitse a cikin jiki. Survodutide kuma na iya yin tasiri ga metabolism na makamashi da nauyin jiki ta hanyoyin kai tsaye kamar daidaita microbiota na gut.
4. Aikace-aikacen Survodutide a cikin Maganin Kiba
4.1 Shaidar Bincike na asibiti
A cikin nazarin marasa lafiya tare da nau'in 2 na metabolism da kiba, Survodutide kuma ya nuna kyakkyawan tasirin hypoglycemic da asarar nauyi. Bayan makonni 16 na jiyya, matakan haemoglobin A1c (HbA1c) na marasa lafiya sun ragu sosai, tare da raguwa mafi girma na 1.7%, kuma nauyin jiki kuma ya ragu sosai, tare da matsakaicin raguwa na 14.9%. A cikin nazarin marasa lafiya da ke da alaƙa da steatohepatitis (MASH) da kuma kiba, Survodutide ba kawai inganta alamun tarihin hanta ba amma kuma ya haifar da asarar nauyi a cikin marasa lafiya. Waɗannan karatun sun ƙara tabbatar da ingancin Survodutide a cikin mutane daban-daban tare da yanayin da ke da alaƙa da kiba.
4.2 Abubuwan Kwatancen Kwatancen Sama da Sauran Magunguna
Idan aka kwatanta da magungunan asarar nauyi na gargajiya, Survodutide yana ba da fa'idodi da yawa. Magungunan asarar nauyi na al'ada sukan yi niyya ga injin guda ɗaya, yana haifar da iyakancewar inganci da babban haɗarin illa. Survodutide, duk da haka, yana aiki ta hanyar ƙwannafi mai karɓa na dual, yadda ya kamata rage nauyin jiki yayin da lokaci guda ke haɓaka sigogi na rayuwa kamar glucose na jini, matakan lipid, da hawan jini, ta haka ne ke ba da cikakkiyar rigakafi da magani don matsalolin da ke da alaƙa da kiba.
Idan aka kwatanta da sauran novel magunguna na asarar nauyi kamar GLP-1 (GLP-1 agonist mai karɓa), a cikin gwaje-gwajen dabba, duka Survodutide da GLP-1 sun haifar da asarar nauyi. Koyaya, Survodutide ya nuna ƙarin tasiri na musamman akan abubuwan zaɓin abinci da rashin daidaituwa na lipid. GLP-1 yana rage cin abinci a farkon matakan jiyya amma yana komawa zuwa matakan asali daga baya, yayin da Survodutide ya ci gaba da rage yawan cin abinci mai kitse da ruwa mai fructose sama da lokacin jiyya na mako 5. Game da bayanan martaba na lipid, GLP-1 da farko yana rage jimillar cholesterol ta hanyar rage HDL-cholesterol, yayin da Survodutide yana nuna raguwar cholesterol a duk abubuwan da ke cikin lipoprotein, gami da LDL-cholesterol. Wannan yana ba da shawarar cewa Survodutide na iya ba da ingantaccen tasiri a cikin daidaita abubuwan abinci da bayanan martaba.
5. Kammalawa
Survodutide, a matsayin sabon agonist dual agonist na GCGR/GLP-1R, yana nuna tasiri mai mahimmanci a cikin maganin kiba. Ba wai kawai yana rage nauyin jiki yadda ya kamata ba kuma yana inganta rarraba kitse na jiki amma kuma yana daidaita daidaitattun sigogin rayuwa kamar su glucose na jini, lipids na jini, da hawan jini, yana ba da fa'idodi masu yawa ga marasa lafiya da kiba.
Sources
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[5] Her MBU, Rosenstock J, Hoefler J, et al. Sakamakon amsa-kashi akan HbA1c da rage nauyin jiki na survodutide, dual glucagon/GLP-1 agonist mai karɓa, idan aka kwatanta da placebo da alamar GLP-1 a cikin mutanen da ke da nau'in 2 metabolism: gwajin gwaji na asibiti [J]. Diabetologia, 2023,67:470-482.
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