▎ Okunoonyereza ku Survodutide
Survodutide evudde mu kunoonyereza kuliwa?
Obunene bw’endwadde z’enkyukakyuka mu mubiri:
Olw’amangu g’obulamu n’enkyukakyuka mu nsengeka y’emmere, endwadde z’enkyukakyuka mu mubiri nga omugejjo, ssukaali ow’ekika eky’okubiri, n’obulwadde bw’ekibumba obutali bwa mwenge (NASH) bifuuse okusoomoozebwa kw’ebyobulamu by’abantu mu nsi yonna. Okugeza, obungi bw’obulwadde bw’ekibumba obukwatagana n’enkyukakyuka y’emmere (MAFLD) busukka ebitundu 30%, era kiteeberezebwa nti omwaka 2030 we gunaatuukira, obulwadde bw’ekibumba obukwatagana n’obutakola bulungi mu mubiri (MASH) bujja kufuuka ekikulu ekivaako okusimbuliza ekibumba, ekissa omugugu omunene ku nkola y’ebyobulamu.
Ebikoma ku ddagala eririwo:
Eddagala ly’ekinnansi erya GLP-1 lirina obuzibu obumu mu kujjanjaba endwadde z’enkyukakyuka mu mubiri. Ku balwadde abamu, ekizibu ky’okugejja tekimatiza, oba bayinza okufuna ebizibu mu lubuto n’ekyenda. Ekirala, obusobozi bwazo okulongoosa enkola y’amasavu mu kibumba butono, era okugumiikiriza kuyinza okukula nga zikozesebwa okumala ebbanga eddene.
Ebirungi ebiri mu Dual Agonists:
Nga agonist ey’emirundi ebiri ey’ekirungo kya glucagon-like peptide-1 receptor (GLP-1R) n’ekirungo kya glucagon receptor (GCGR), Survodutide esobola okulungamya enkyukakyuka y’emmere okuva mu bipimo ebingi. Okuyita mu kkubo lya GLP-1R, esobola okuziyiza okwagala okulya, okulwawo okufulumya amazzi mu lubuto, n’okutumbula okufulumya insulini okukendeeza ku glucose mu musaayi. Okuyita mu kkubo lya GCGR, esobola okutumbula omukka gwa asidi w’amasavu mu kibumba, okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, n’okulongoosa butereevu fibrosis y’ekibumba, nga kiraga ebikolwa ebirungi eby’obujjanjabi ku mugejjo, ssukaali, n’endwadde z’ekibumba mu kugezesa ebisolo.
Enkola ya Survodutide ekola ki?
1. Agonism ya Receptor ey’emirundi ebiri
Survodutide ye agonist ey’emirundi ebiri ey’ekirungo kya glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R).
GLP-1R Obulwadde bwa Agonism
Oluvannyuma lw’okukola ekirungo kya GLP-1, kisobola okutumbula okufulumya insulini eyeesigama ku glucose n’okuziyiza okufulumya glucagon, bwe kityo ne kikendeeza ku mutindo gwa glucose mu musaayi. Survovudutide bw’ekola GLP-1R, esobola okutumbula okufulumya insulini okuva mu butoffaali bwa β obw’ekizinga ky’olubuto era, mu kiseera kye kimu, ekendeeza ku kufulumya glucagon obutoffaali bw’ekizinga ky’olubuto α, okutuuka ku kulungamya okulungi okwa glucose mu musaayi [1]..
Okugatta ku ekyo, GLP-1R gonism era esobola okulwawo okufulumya amazzi mu lubuto n’okwongera okuwulira ng’ojjudde, bwe kityo ne kiyamba okukendeeza ku mmere gy’olya n’okufuga obuzito bw’omubiri.
GCGR Obulwadde bwa Agonism
Okukola ekirungo ekikwata glucagon kiyinza okwongera okukozesa amaanyi n’okutumbula okumenya amasavu. Survodutide esitula GCGR, okwongera ku mutindo gw’amasoboza g’omubiri n’okuleetera okumenyaamenya triglycerides mu bitundu by’amasavu okufuuka asidi z’amasavu ne glycerol, okuwa ensibuko y’amasoboza eri omubiri [1]..
2. Ebikosa Enkyukakyuka y’Emibiri
Okulongoosa mu nkyukakyuka ya Glucose
Survovudutide ekendeeza nnyo ku mutindo gwa glycated hemoglobin (HbA1c). Mu kunoonyereza okwakolebwa, abalwadde ba sukaali ow’ekika eky’okubiri abajjanjabwa n’eddagala lya Survovudutide baalaga okukendeera okw’amaanyi mu miwendo gya HbA1c oluvannyuma lwa wiiki 16 nga bajjanjabiddwa. Okugeza, bw’ogeraageranya ne semaglutide, Survovudutide (DG2) eya dose entono yalina kye yakola mu kukendeeza HbA1c. Omuwendo gwa HbA1c mu kibinja kya DG2 gwakendeera 15.95 mmol/mol (-1.46%), ate ogw’ekibinja kya semaglutide gwakendeera 16.07 mmol/mol (-1.47%) [1]..
Enkola yaayo ey’okukola eyinza okutuukibwako nga eyongera ku kufulumya insulini, okuziyiza okufulumya kwa glucagon, n’okulongoosa okutwalibwa n’okukozesa glucose ebitundu ebiriraanyewo.
Okulungamya Enkyukakyuka y’Amasavu
Survovudutide esobola okukendeeza ku masavu mu musaayi. Mu kunoonyereza okwakolebwa ku balwadde abagejjulukuka, bw’ogeraageranya n’eddagala erya placebo, Survodutide yakendeeza nnyo ku mutindo gwa triglyceride (TG), era n’ekendeeza ku miwendo gya low-density lipoprotein (LDL), total cholesterol (TC), ne non-high-density lipoprotein cholesterol (non-HDL-C) mu bibinja ebimu ebya dose [2] ..
Mu kiseera kye kimu, Survodutide era esobola okukendeeza ku masavu mu kibumba. Mu kunoonyereza okwakolebwa ku balwadde abalina obulwadde bwa metabolic dysfunction-associated steatohepatitis (MASH), ekitundu ky’abalwadde abajjanjabwa n’eddagala lya Survovudutide nga amasavu mu kibumba gakendedde waakiri ebitundu 30% kyali kinene nnyo okusinga mu kibinja kya placebo. Okugeza, 63%, 67%, ne 57% ku balwadde mu bibinja bya Survovudutide 2.4mg, 4.8mg, ne 6.0mg, okusinziira ku, baatuuka ku kiraga kino, ate 14% bokka mu kibinja kya placebo [3]..
3. Ebikosa Enkola y’emisuwa gy’omutima
Okulongoosa ensonga ezireeta emisuwa n’emisuwa
Survovudutide esobola okukendeeza puleesa. Mu balwadde abagejjulukuka, bw’ogeraageranya n’eddagala erya placebo, puleesa zombi eza systolic blood pressure (SBP) ne diastolic blood pressure (DBP) zakendeera nnyo oluvannyuma lw’okujjanjabwa ne Survodutide. Mu bujjanjabi obwennyini, Survodutide esobola okukendeeza ku SBP okutuuka ku mmHg 10.2 ne DBP mmHg 4.8, era ekikolwa ekikendeeza puleesa kifaanagana awatali kulowooza oba omulwadde yalina puleesa nga tannakeberebwa [2]..
Ng’oggyeeko ekyo, Survodutide era esobola okukendeeza ku kwetooloola ekiwato. Mu balwadde abagejjulukuka, okwetooloola ekiwato kw’abalwadde mu bibinja byonna ebya dose ya Survodutide kwakendeera, era ekibinja kya 4.8mg kye kyasinga okukendeera wakati, nga kino kyali sentimita 16.6 [2]..
Ebikosa obubonero bw’obulwadde bwa Steatohepatitis obutali bwa mwenge (NASH) .
Survovudutide eyinza okuba n’ekikolwa ekirongoosa ku bubonero obumu obw’obulwadde bwa steatohepatitis obutali bwa mwenge (NASH). Okunoonyereza okuliwo kati kulaga nti Survodutide eyinza okukola kinene mu kuziyiza enkula ya NASH ng’elongoosa enkyukakyuka y’amasavu mu kibumba n’embeera y’okuzimba [4]..
Survodutide ekozesebwa ki?
1. Obujjanjabi bwa sukaali ow’ekika eky’okubiri n’omugejjo
Nga eddagala erikola okumala ebbanga eddene ery’emirundi ebiri, Survodutide eweebwa omulundi gumu mu wiiki era eraga nti ekola kinene mu kujjanjaba obulwadde bwa sukaali obw’ekika eky’okubiri (T2DM) n’omugejjo.
Okukendeeza ku Glycated Hemoglobin (HbA1c):
Okugezesebwa okungi kulaga nti Survodutide esobola bulungi okukendeeza ku muwendo gwa HbA1c mu balwadde. Okugeza, mu kunoonyereza okwakolebwa ku balwadde ba T2DM, oluvannyuma lwa wiiki 16 nga bajjanjabwa, omuwendo gwa HbA1c gwakendeera okutuuka ku bitundu 1.7% [4] . HbA1c kiraga kikulu ekiraga okufuga glucose mu musaayi okumala ebbanga eddene, era okukendeera kwayo kitegeeza nti okufuga glucose mu musaayi kw’omulwadde kulongooseddwa.
Okugejja okw’amaanyi:
Ku balwadde abalina T2DM n’omugejjo, Survodutide esobola okutuuka ku kugejja okutuuka ku bitundu 14.9% mu wiiki 46 ez’obujjanjabi [4] . Kino kikulu nnyo eri abalwadde abatawaanyizibwa okugejja okutera okuva ku ddagala ly’ekinnansi eritta ssukaali. Okugejja tekikoma ku kuyamba kulongoosa ndabika y’omulwadde n’omutindo gw’obulamu bwe wabula kikendeeza n’obulabe bw’okufuna ebizibu ng’endwadde z’emisuwa.
2. Okulongoosa ensonga ezireeta emisuwa n’emisuwa
Survodutide era erina akakwate akalungi ku bintu ebiyinza okuvaako emisuwa gy’omutima.
Okukendeeza Puleesa:
Mu kugezesebwa okw’obujjanjabi ku balwadde abagejjulukuka, bw’ogeraageranya n’eddagala eriyitibwa placebo, Survodutide esobola okukendeeza ku puleesa y’omusaayi (systolic blood pressure) okutuuka ku mmHg 10.2 ne puleesa y’omusaayi (diastolic blood pressure) okutuuka ku mmHg 4.8 [2] . Okukendeeza puleesa kikulu nnyo mu kuziyiza endwadde z’emisuwa naddala eri abalwadde abagejjulukuka ne puleesa.
Okulongoosa mu bipimo by’amasavu mu musaayi:
Survodutide esobola okukendeeza ku mutindo gwa triglyceride (TG) era era erina ekikolwa ekimu eky’okulongoosa ku bipimo by’amasavu mu musaayi nga high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), ne non-high-density lipoprotein cholesterol (non-HDL-C) [2] . Okugeza, mu bujjanjabi obwali butegekeddwa, TG eya wakati mu bibinja byonna ebya Survodutide yakendeera nnyo.
3. Obujjanjabi bw’obulwadde bwa Steatohepatitis obutali bwa mwenge (NASH) .
Survodutide era eraga obusobozi mu kujjanjaba obulwadde bwa steatohepatitis obutali bwa mwenge (NASH).
Okulongoosa mu bitundu by’ekibumba:
Mu wiiki 48, phase 2 clinical trial ku balwadde abakulu abalina MASH (metabolic dysfunction-associated steatohepatitis) ne liver fibrosis, Survodutide yali esinga placebo mu kulongoosa MASH awatali kwongera kuzimba kibumba. Okusingira ddala, mu balwadde abajjanjabwa ne dose ez’enjawulo eza Survodutide, abalwadde 47% mu kibinja kya 2.4mg, 62% ku balwadde mu kibinja kya 4.8mg, ne 43% ku balwadde mu kibinja kya 6.0mg baalaga okulongoosa mu MASH, ate 14% bokka mu kibinja kya placebo [3]..
Okukendeeza ku masavu mu kibumba:
Survodutide era esobola okukendeeza ku masavu mu kibumba. Mu kugezesebwa okw’obujjanjabi okwayogeddwako waggulu, 63%, 67%, ne 57% ku balwadde abajjanjabiddwa ne dose za Survodutide 2.4mg, 4.8mg, ne 6.0mg, okusinziira ku, baalina okukendeera mu masavu mu kibumba waakiri 30%, so nga 14% bokka mu kibinja kya placebo [3]..
Okulongoosa mu bulwadde bwa Liver Fibrosis:
Okugatta ku ekyo, alongoosezza obulwadde bw’ekibumba okutuuka ku ddaala eritali limu. Mu kugezesebwa kuno, 34%, 36%, ne 34% ku balwadde abajjanjabwa ne dose za Survodutide 2.4mg, 4.8mg, ne 6.0mg, okusinziira ku, baalaga okulongoosa mu fibrosis y’ekibumba waakiri omutendera gumu, so nga yali 22% mu kibinja kya placebo [3]..
4. Enkola ku mmere gye yeegomba n’okulongoosa mu buzibu bw’amasavu mu musaayi
Mu nkola ya hamster omugejjo, byombi Survodutide n’eddagala eddala, Semaglutid, bisobola okuleeta okugejja n’okukendeeza ku insulin resistance index (HOMA-IR), naye birina ebikosa eby’enjawulo ku mmere gye yeegomba n’okukendeera kw’amasavu mu musaayi.
Enkola y’Emmere y’Okulya:
Semaglutid yakendeeza nnyo ku kulya emmere eya bulijjo n’emmere erimu amasavu amangi mu wiiki esooka ey’okujjanjabwa naye oluvannyuma n’edda ku muwendo ogwasooka. Mu kiseera kye kimu, kyayongera nnyo ku mazzi aga bulijjo n’okukendeeza ku mazzi agalimu ekirungo kya fructose. Okwawukanako n’ekyo, Survodutide teyakyusa mmere ya bulijjo n’amazzi aga bulijjo naye yakendeeza nnyo ku mmere erimu amasavu amangi n’amazzi agalimu fructose mu kiseera ky’okujjanjaba ekya wiiki 5 [5]..
Enkola y’amasavu mu musaayi:
Semaglutid ne Survodutide byombi bisobola okukendeeza ennyo ku muwendo gwa kolesterol gwonna mu plasma, nga bikendedde ebitundu 24% ne 41%, okusinziira ku. Okukendeeza ku muwendo gwa kolesterol gwonna nga Semaglutid kyavaako okukendeera kwa 25% mu muwendo gwa kolesterol ogwa high-density lipoprotein, naye omuwendo gwa kolesterol ogwa low-density lipoprotein tegwakyuka. Enkola ya Survodutide ekendeeza kolesterol yalabibwa mu bitundu byonna ebya lipoprotein, omuli n’okukendeera kwa 39% mu kolesterol wa low-density lipoprotein [5]..
Mu kumaliriza, nga dual receptor agonist, Survodutide esobola okulungamya enkyukakyuka mu mubiri, okukendeeza ku glucose mu musaayi, okukendeeza ku buzito bw’omubiri, okulongoosa ensonga z’obulabe eri emisuwa gy’omutima, n’okulongoosa obubonero bw’obulwadde bwa steatohepatitis obutali bwa mwenge. Ewa ebirowoozo ebipya ku kujjanjaba endwadde ezikwatagana era ya makulu nnyo mu kulongoosa omutindo gw’obulamu bw’abalwadde.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Le Roux C munoonyereza alina akakwate n’ebibiina ebiwerako. Mu bino mulimu Yunivasite y’e Dublin, St Vincents Uni Hosp, Ulster University, Eddwaaliro lya Saint Vincent’s University Hospital, St Vincents Hosp Grp, KU Leuven, Eddwaaliro lya Yunivasite Leuven, Conway Inst Univ Coll, Ctr Diabet, Inst Conway, Yunivasite y’e Gothenburg, Imperial College London, ICL, Univ Dublin, Istituto per la Sintesi Organica e la Fotoreattivita (ISOF-CNR), Yunivasite y’e Maastricht, eddwaaliro lya King’s College, eddwaliro lya King’s College Hospital NHS Foundation Trust, eddwaaliro lya Musgrove Park n’eddwaliro ly’eggwanga erikola ku by’obusimu n’okulongoosa obusimu.
Ebintu by’anoonyerezaako bingi - bikwata ku kulongoosa, Endocrinology & Metabolism, Nutrition & Dietetics, Oncology, ne Biochemistry & Molecular Biology. Omulimu gwe mu bintu bino gulaga obukugu bwe bungi n’ebintu ebikulu by’akoze mu kutumbula ssaayansi w’obusawo. Le Roux C ewandiikiddwa mu kiwandiiko ekijuliziddwa [2].
