596
5223922001003471
|350220010019
VNITŘNÍ4268040010746106127172220280301
LÉKAŘSTVÍ748804001074185130188236280325378400
/11948040010731
Vnitř1270804001074693112140166
Lék.1456804001074083122140
2025;71(1):51-571615804001074487129173186227268286326344358403442465508550
/22108040010731
www.casopisvnitrnilekarstvi.cz442680400107651332012142542953293774274464795215705896176436927117307748128548809159449871007102310631101
FARMAKOLOGICKÝ42522001003983129195242289338373423469489529576625
PROFIL106522001004388139179198233
Tirzepatid4253300100365377110144182218244260298
–739330010038
slibný794330010028435896134170
lék9803300100155084
pro108133001003761100
kardiovaskulární11973300100336993131146185220256285319357373407431470485
protekci169833001003862100126161196225240
a1955330010033
léčbu20053300100145081119157
diabetu21783300100375387125161188226
a2421330010033
obezity247133001003776111143159185224
specifické42562001073483128169188212232272310353
účinky80562001074888107155193236
obou106762001074898147196
inkretinových128962001071967105133176204223271319360403443491
hormonů,180662001074997124199247296344359
především219162001075077120170214255289307381
v2598620010741
oblasti266562001074898118159192221240
ovlivnění42576001074888108126167216260308327
tělesné7727600107277089133167214258
hmotnosti1050760010748122170198246295328357376
(4).14467600107236586100
Molekula565900010770118137180218266285325
tirzepatidu9069000107284672110153202243270288337384
byla130690001074988108148
navržena147090001074888128155193235283323
tak,180990001072869106124
aby194990001074190129
jeho209490001072063111159
afinita22699000107416483131149177217
k2503900010738
receptoru255790001072669109151201228274301348
GIP425104001075574118
byla558104001074987107146
řádově720104001072666114162201243
srovnatelná978104001073359105144192231257299317364404
s13971040010733
afinitou144610400107406382129146174219266
přirozeného172810400107497593118164199241288331378425
GIP,2169104001075573117121
kdežto2306104001073785128164194239
jeho2561104001071961108156
afinita273210400107406382129147425118001072868
k5091180010738
receptoru562118001072769109151200227273299347
pro924118001075076122
GLP-11062118001075695140165203
je1281118001071962
přibližně135911800107497594143162180215263306
5×1681118001074493
slabší,179011800107335191140173190205
než2011118001074891128
má21541180010773113
endogenní2283118001074391139187236279327374392
GLP-1.2691118001075595139165203214
Polypeptidová425132001074592112152203248298325344394442483525
sekvence976132001073478116161204252293336
tirzepatidu133813200107284774112156205247274293343391
má17551320010774115
potom18961320010750100127174248
stejnou2171132001073463105124173221270
aktivitu2467132001074179110129170190218267
jako276013200107196098146
nativní425146001074889116135176225243
molekula6871460010774122142186224272291332
GIP,1038146001075675120125
ale1181146001074160104
je1304146001071963
méně13861460010774118166210
účinná1615146001074888106154202243
v18771460010740
oblasti1936146001074898118158192221239
GLP-12194146001075697142168207
receptoru.2420146001072669110153203230277304352368
Na2807146001075798
polypeptid425160001075099119159209254304331350399
je848160001072064
navázán936160001074889128170207249298
dvojřetězec1258160001074990137156183225253296333376417
C201699160001075196139
nenasycené1863160001074892140181214255295337385430
mastné23171600010774114148177225269
kyseliny,2611160001073881114159178196244283294
která425174001073869111138180
umožní6241740010748122170206254273
prolongovaný917174001074976123143191240289337378419467506
účinek1443174001074788106154198236
s16991740010734
dávkováním1752174001074990130168216256297346364438
jednou2209174001072063113161210258
týdně2487174001072870119167211
(5).271817400107236688102
Hodnocení4251990013876139203267330380438502535
účinku9971990013861112145209272336
a13701990013858
klinické1450199001386194127191224274338396
studie1883199001384993157221254313
Výsledky565216001074687121140184234272314
prvních903216001074976120169188228276
studií1202216001073362110160179197
fáze1422216001072466103146
IIb159121600107193887
tohoto1702216001072774123171198245
léku1970216001071963101150
(pod2143216001072474123173
kódovým2339216001073886136184224267342
označením2704216001074883132173425230001074185135154230
LY3298176)683230001074182127170214260302340382405
byly1116230001075192112154
poprvé12982300010751101153181227272
publikovány15982300010751101152172192231280322365415455
na2080230001075092
kongresu2200230001073988138189217261296345
Evropské2573230001074384113162213248287332
asociace425244001074174122164182223263306
pro747244001075077124
studium888244001073362110159178225299
diabetu1204244001074967107157202230278
(EASD)1498244001072466120163220242
v17562440010741
Berlíně1814244001074590116136154202246
v20772440010740
roce2134244001072774115157
2018,2308244001074487127166182
v25062440010741
roce2564244001072673115157
20212738244001074487128167
byla425258001075089109149
ukončena592258001074886133182222264312353
série963258001073377104123167
studií1148258001073362110159178197
III.13622580010719385773
fáze1453258001072365103145
klinického161625800107385977125143184222265313361
hodnocení1995258001074897147195243284327375394
léku2406258001071963101150
v25732580010741
indikaci2631258001071967116135173215256274
diabetes425272001074866106154198225267300
mellitus7412720010772116134152170197244277
2.1033272001074458
typu1107272001072869119166
s12892720010733
označením1338272001074782130169209250297315387
SURPASS.1741272001074195140184230273312328
Na2085272001075696
základě2197272001073677114134174222265
výsledků2478272001074083116134177226263310
tohoto2804272001072773425286001074795121166
hodnocení607286001074795143190238278319366384
byl1006286001074987106
tirzepatid112828600107274571108150198239265283331
schválen1475286001073372119157198216259306
pro1796286001074975121
použití1932286001074997144180198225243
u21912860010747
pacientů2254286001074889128146189236262308
s25782860010733
DM226262860010758126169
jak281028600107195895
Úřadem425300001075682123172216290
pro731300001075076123
kontrolu871300001073885133160186233253300
potravin1187300001075099126153194234253301
a15043000010741
léčiv1561300001071963104122163
v17413000010740
USA1798300001075696147
(FDA1962300001072465121171
=21503000010753
U.S.2220300001075670112128
Food2365300001074188137187
and2568300001074189138
Drug2723300001075885133182
Administration),4253140010753102176195243262295324351393421440488537559573
tak1024314001072870109
posléze11593140010750100134153197234278
i14633140010719
Evropskou1509314001074282110158208242280328376
lékovou1912314001071963102150190238287
agenturou2225314001074191136184212260287334383
(EMA2634314001072466137190
=28513140010754
European425328001074187113159208252292339
Medicines7803280010769113162180219237285328361
Agency).11573280010752100143190230272294306
V14793280010745
sérii1540328001073477103122140
studií1696328001073361108157175193
s19053280010733
označením1954328001074782130170210251299317389
SURMOUNT2359328001074195140209269324381423
byl2798328001074988107
tirzepatid30476200107284773112154204246273292341
testován340662001072770104133179220261309
v3733620010741
léčbě379262001071963104153198
obezity400862001074898143180199227270
a4296620010741
nadváhy435562001074889138179221269307
(u468062001072469
diabetiků476762001074968108158202230249287335
i5120620010719
nediabetiků).515762001074892142161201251296323342304776001073886108121
Posléze318776001074692125144188225268
již34757600107193874
v3569760010741
rychlém362976001072770109157176220294
sledu39437600107335296146193
byly415676001075089109149
publikovány432576001074998147167185223270310352400438
studie,478376001073463111160179222237
hodnotící504076001074896146194243270289329348
vliv54077600107416179120
tirzepatidu30479000107274571108150198239265283331377
na344090001074787
syndrom354290001073373121169195241313
spánkové387190001073380121168205251290332
apnoe,421890001074189136183227241
chronické447490001074087112158205223262299341
onemocnění483090001074795138210257297344387434451
ledvin,529790001071962110150169216230
metabolicky30471040010774118146187237286306324364402445
asociovanou3510104001074174123164183231271312360409457
steatohepatitidu3985104001073463105145172219268312362403430449477496545593
a45961040010741
další4655104001074989108141159
syndromy,4832104001073475124174200247321360371
a52211040010741
potom5280104001075099127173247
především3047118001075076119169213254288306380
na3446118001074989
kardiovaskulární3555118001073880107155174222262303337374422441482508557576
systém.4150118001073475109138180254270
Studie30471430013858101165230263322
SURPASS34061430013857134204274344406466
„3047161008960
SURPASS3187160001074297142188235278318
1:3524160001074454
měla35971600010774118137177
za3793160001073779
úkol3891160001074785133152
hodnotit4062160001074897147195243271289317
účinnost4398160001074888107155203251285314
a47311600010740
bezpečnost4790160001075095132182227268316365398427
aplikace5236160001074190110128166208249292
tirzepatidu318717400107284671109151200241268286334381
u35841740010747
nedostatečně3647174001074791140187220249289316357398445488
kompenzovaných4151174001073784157205250297333379419460507544583631
pacientů4797174001074990130148191238265312
s51241740010734
DM2,51741740010757126169184
kteří5373174001073868110136154
nebyli3187188001074892142181201220
nikdy3428188001074867104153193
léčeni3642188001072064105147195214
injekční387718800107196785129167206254273
antidiabetickou4171188001074189116135184203243292337365384424462509558
terapií.475018800107287097138188207226241
545013188001074488
%51221880010767
pacientů5210188001075091132150194242269317
bylo3187202001075089108156
jen3360202001071963111
na3487202001074889
dietě,3592202001074968111139181195
ostatní3804202001074881110151178226245
užívali4065202001074884103144186204223
v43042020010741
minulosti4361202001077492140187206254287316335
perorální4712202001075095121168195236255303321
antidiabetika,5049202001074189116134183202242291336364383420462478
ale3187216001074160104
v33162160010741
době3382216001074997148192
zařazení3600216001073678105146183226274293
do3918216001074997
studie4041216001073362110160178222
je4289216001071963
již437721600107193874
neměli.4477216001074892166210229247263
Celkem4766216001075194113150193267
4785058216001074485127
pacientů5210216001075091132151194243269317
(483187230001072464109
%33122300010765
žen,3393230001073678126141
průměrný3549230001075076123196239265313350
věk3915230001074083120
54,14051230001074387101139
let,420623000107196289105
průměrný4327230001074975123195238264312350
vstupní4693230001074073102149197245263
HbA1c49722300010756105156512123600632546
635184230001074385
mmol/52842300010773145193212244
mol,31872440010774122142157
trvání336624400107285599140188207
diabetu3595244001074968108158203231279
průměrně3896244001075076125198242269317361
4,74280244001074458102
roku,4404244001072774112161176
průměrný4602244001075077125199243269318356
BMI49812440010745115134
31,9513824400107448293135
kg/m2)5288244001073887119191547824400632655042440010724
bylo3187258001074987107154
randomizováno3356258001072767114162210282300336382421462509556
k39282580010737
podávání3981258001074997146186225265312330
5,4327258001074356
10,439925800107438296
nebo4511258001074790139187
154714258001074380
mg48092580010772121
tirzepatidu494525800107284671109151200240267285333379
nebo5340258001074791139187
placeba3187272001075069110150193243284
jednou3491272001071963113161210258
týdně,3769272001072871119167211226
přičemž401527200107497695135178251288
dávkování4323272001074990129168215256297345364
tirzepatidu470727200107284773111154204246273292341388
bylo5115272001075089109157
zvyšováno52922720010737811241582063187286001074182130179
po3386286001074999
2,53505286001074459103
mg36242860010774123
dávkách3767286001074990129168210251299
každé4086286001073881118166210
čtyři4316286001074070113140159
týdny.4495286001072871119167206218
Po4733286001074591
404844286001074490
týdnech4954286001072870119167211252300
užívání5274286001074885104145187235253
tirzepatid318730000107284876116160211254283302353
vykázal3568300001074286126170209253273
superioritu3868300001073583134181208229278306327356405
vůči4301300001074292132152
placebu4480300001075172114156200251301
v48093000010741
ovlivnění4878299001105299124148196250299353377
HbA1c,5282299001106211717654523060065295255062990011022
glykemie3187313001105275121168214291314361
nalačno,3568313001105298121168209261312333
tělesné3921313001103278102149188240287
hmotnosti42283130011051128179212263315352385408
i46583140010719
v46983140010741
podílu4760314001075099149168189236
pacientů,5017314001075092132151195243270317333
kteří5371314001073869111138157
dosáhli3187328001074895127167214232249
snížení345132800107337997132173220238
HbA1c37043280010755103153385033400632546
pod3911328001074996145
534071328001074383
mmol/mol,41683280010772144191209240310357375389
ba4572328001074989
dokonce4676328001074895132178225264305
i49963280010719
pod5030328001074896144
395189328001074384
mmol/52873280010772144191209240
His5324040081446087
His23864310081446087
His23854890081446087
Ala6704040081415789
Ala30594600081415789
Ala43354350081415789
Ala50264640081415789
Ala47574980081415789
Ala40684550081415789
Ala22274010081415789
Met290443100815488110
Ala30524310081415689
Ala6484360081415789
Ala7814360081415789
Lys5284430081326187
Lys14504640081326187
Lys26484310081326187
Lys32944670081326187
Lys30504890081326187
Lys31854890081326188
Lys46184350081326187
Lys40744420081326187
Lys25154890081326187
Ala9134640081415789
Glu7984040081435996
Glu23674010081435996
Glu11794360081435996
Leu130943600813264101
Leu278246000813264101
Leu489843600813264101
Leu474046500813264101
Leu291746000813264101
Leu118246400813264101
Glu5264570081435996
Gly9384040081435991
Gly25034010081435991
Gly10504360081435991
Gly15894640081435991
Gly32924800081435991
Arg167947300814163100
Gly16814870081435991
Gln9154360081435996
Gln31824600081435996
Gln41944360081435996
Gln44534640081435996
Gln22474310081435996
Gln22235180081435996
Gln21344380081435996
Thr10724040081337092
11106539200813469
GLP-1108238000814375110130164
GIP27063780081435995
Tirzepatide4525378008133487099132171203225240278312
C20364241700813973108
diacicd-γ-Glu-(AEEA)37644170081385385115131161199219250271316331368389408448481514555573594
16181240500813469
52659390008134
54641391008134
10340240200813469
10539840500813469
15278042000813469
15476442400813469
20203943100813469
20398243500813469
25265744800813469
25460745300813469
30340145800813469
30540546800813469
35279747700813469
35477448500813469
40204248500813469
21118742400813469
2644943500813469
31105845400813469
36181246800813469
Phe119640400813672106
Tyr14504360081336284
Tyr20964010081336284
Tyr32874090081336284
Trp26534600081335291
Trp45994650081335291
Trp26554890081335291
Trp10524640081335291
Phe63946400813672106
Phe277540100813672106
Phe224146000813672106
Ile7924640081163266
Ile29254010081163266
Ile25304310081163266
Ile21594960081163266
Ile31964310081163266
Ile51804350081163266
Ile44884350081163266
Ile48984650081163266
Thr13434040081337092
Thr26484010081337092
Aib41804020081415695
Aib50364360081415695
Glu43194020081435996
Gly44654020081445991
Gly51684640081435991
Gly48974990081435991
Gly52814730081435991
Tyr40464020081336284
Tyr52804120081336284
Phe474940200813672106
Pro52754880081365693
Pro43304990081365693
Pro44734990081355692
Pro46134990081365692
Phe416446400813672106
Thr46134020081337092
Thr48984020081337092
Thr21365100081337092
Ser14764040081336789
Ser30494010081336789
Ser50434020081336789
Ser52894270081336789
Ser51914980081336789
Ser41844990081336789
NH3946497009451102127
–4089497009439
Ser50464990081336789
Ser32874220081336789
Ser16964270081336789
Ser15864360081336789
Asp160540400814167105
Asp211245200814167105
Asp277548900814167105
Asp317540100814167105
Asp517840200814167105
Asp474943500814167105
Asp278043100814167105
Asn251146000814167104
Asn224148900814167104
Asn291048900814167104
Val16954130081376783
Val13214640081376783
Val23854600081376783
Val43224640081376783
Obr.4253550011362114150173
1.625355001135478
Srovnání731356001073964108146192237283301
molekuly10483560010772117136174211256275312
GLP-1,1376356001075389132158195206
GIP1598356001075371114
a17283560010745
tirzepatidu;178935600107274570107144189235261279324370384
upraveno2189356001074691117160198235281326
podle2531356001074691138156194
(1)274135600107246179
↑11816870011376
sekreci1275687001133375113142182218237
inzulinu153168700113196396139158177221265
↑11816980011376
biosyntézu1275698001134463107140176220248288321365
inzulinu165969800113196396140159178222266
↓11817080011376
sekreci1275708001133375113142182218237
glukagonu1531708001133959102141179218262306350
při127771800113441321718001132948
euglykemii1388718001134286125145183221259326346365
a12697280011340
hyperglykemii1337728001134481124166196234253291329368435454473
↑11817380011376
sekrece1276738001133375113142182218260
glukagonu1555738001133958102140179218262306350
při127774800113441321748001132948
hypoglykemii1389748001134480124169208227265303342409428447
↑11817580011376
proliferaci1276758001134473116135154180219249287323342
β-buněk1637758001134416827580011326701141581839758001134218817580011338
↓11817680011376
apoptózu1276768001134084128172200243275319
β-buněk1614768001134416597680011326701141581816768001134218587680011338
pankreas2046745001134484128166195236276309
tuková2014613001132872110151189228
tkáň226161300113286610423656130011344
CNS2125671001134599137
kost3766632001133879112139
žaludek374469100113333775691001134059103147189227
systémový4029714001133369101129169236280318356
efekt4029724001134267106145172
↓41436600011376
vyprazdňování423866000113387612015018822144586600011344884546660001134481121165184
žaludku414467000113334175670001134059103147185228
↓40357470011376
hyperglykemii4130747001134480124166195234253291329368435454473
↑40357570011376
citlivost413075700113355482101120158202235262
k44117570011338
inzulinu446875700113196396140159178222266
↑39715870011376
formaci406658700113266897164204240259
kosti43445870011338801124455587001132347
↓39715970011376
resorpci4066597001132970103147176220255274
kosti43605970011338791124471597001132347
↑14025850011376
lipogenezi149758500113193882126166207251293326344
↑12296300011376
proliferaci1323630001134473116135154180219249287323342
progenitorových1325640001134473116156197241260288332361404441480514558
buněk13256500011344881321457650001134214996500011338
↓12296600011376
příjem1324660001134413686600011329481416660001132062129
jídla156466000113203983102142
TIRZEPATID2852665001555585148201256316375421451521
Obr.4255540011362114150173
2.625554001135481
Účinky733555001075490108154190230
tirzepatidu;97955500107264470106143189235261279324369383
upraveno1379555001074591117159197234281326
podle1721555001074591137156194
(2)193155500107246385