UDA1LS

SLCW WAvL SLLL 1PL 8lSk Cl 1?L 2 ulA8L1LS

CcLober 20 200
Cvervlew
1he body requlres slowwave or deep resLoraLlve sleep Lo malnLaln healLh Slowwave sleep
occurs more Lhan half of Lhe nlghL ln humans wlLh long or shorL sleep paLLerns 1he meLabollc changes
leadlng Lo Lype 2 dlabeLes generally assoclaLed wlLh older adulLs and Lhe overwelghL populaLlon has
been llnked Lo Lhe sleep deprlvaLlon of deep resLoraLlve sleep
Sleep SLages
Sleep occurs ln Lwo maln sLages 8LM or rapld eye movemenL sleep and non8LM sleep also
known as slowwave sleep (SWS) 8LM sleep causes hlgh elecLrlcal acLlvlLy ln Lhe braln slmllar Lo Lhe
waklng sLaLe wlLh vlvld dreamlng Laklng place AbouL 73 Lo 80 percenL of sleep Llme of adulLs ls spenL ln
slowwave non8LM sleep Slowwave sleep progresses Lhrough 4 sLages wlLh sLage belng Lhe llghLesL
sleep and sLage 4 belng Lhe deepesL sleep

lmporLance of Sleep SLages
A sLudy publlshed ln Lhe Amerlcan !ournal of sychlaLry dlscusses Lhe bodys need for slow
wave sleep as lL relaLes Lo 8LM sleep 1he sLudy reporLs slowwave sleep occurs ln Lhose who sleep
shorLer hours and Lhose who sleep longer ln relaLlvely equal amounLs of Llme 1he sLudy goes on Lhe say
LhaL Lhe body has a consLanL need for slowwave sleep whereas 8LM sleep dlffers wlLh personallLy and
llfe sLyle
1ype 2 ulabeLes
ulabeLes resulLs when Lhe pancreas does noL produce Lhe hormone lnsulln or does noL produce
enough lnsulln whlch resulLs ln an lncrease ln blood glucose levels 1ype 2 dlabeLes accounLs for 83
percenL of all dlabeLes cases wlLh 90 percenL of Lhose people belng overwelghL accordlng Lo Lhe World
PealLh CrganlzaLlon PealLh care focuses on dleLary changes reduclng welghL and lncreaslng exerclse as
a means Lo LhwarL developmenL of Lhls Lype of dlabeLes
Sleep SLudy
1he poLenLlal rlsk of Lhls ageassoclaLed dlsease has been llnked Lo sleep deprlvaLlon ln a sLudy
performed by unlverslLy of Chlcago researchers ueprlvaLlon of slowwave or deep resLoraLlve sleep
lncreased blood glucose levels ln healLhy men and women sub[ecLs aged 20 Lo 3 Lhe sLudy reporLs 1he
sub[ecLs were dlsLurbed by nolses noL loud enough Lo cause a full awakenlng durlng slowwave sleep
1he sLudy reporLs LhaL 90 percenL of slowwave sleep was losL each nlghL ln all sub[ecLs shlfLlng Lhe sleep
paLLern from deep Lo llghL sleep for mosL of Lhe nlghL each nlghL of Lhe sLudy
Sleep Loss and lnsulln
unlverslLy of Chlcago Medlcal CenLer researchers admlnlsLered lnLravenous glucose Lo Lhe sleep
sub[ecLs afLer each nlghL of slowwave sleep deprlvaLlon AfLer only Lhree nlghLs of slowwave
dlsLurbances lnsulln senslLlvlLy decreased 23 percenL demonsLraLlng an lncrease ln Lhe lnsulln Lhe body
needed Lo breakdown Lhe glucose 1yplcal of aglng chronlc shallow resLoraLlve sleep may conLrlbuLe Lo
meLabollc changes as seen ln Lype 2 dlabeLes Lhe reporL sLaLes



















2 -LW 18LA1ML-1 lC8 1?L 2 ulA8L1LS
March 23 20
roduct komblglyze O8 3/300
ompany 8rlsLolMyers Squlbb
harmaco|og|c c|ass AnLldlabeLlc (dlpepLldyl pepLldase4 (u4) lnhlblLor + blguanlde)
Act|ve |ngred|ents SaxagllpLln 3 mg meLformln PCl exLendedrelease 300 mg LableLs
A|so komblglyze O8 3/000
Act|ve |ngred|ents SaxagllpLln 3 mg meLformln PCl exLendedrelease 000 mg LableLs
A|so komblglyze O8 23/000
Act|ve |ngred|ents SaxagllpLln 23 mg meLformln PCl exLendedrelease 000 mg LableLs
nd|cat|on Ad[uncL Lo dleL and exerclse ln Lype 2 dlabeLes when LreaLmenL wlLh boLh saxagllpLln and
meLformln ls approprlaLe
harmaco|ogy komblglyze O8 ls an anLldlabeLlc producL LhaL comblnes a u4 lnhlblLor and exLended
release form of Lhe blguanlde meLformln SaxagllpLln slows Lhe lnacLlvaLlon of lncreLln hormones
lncreaslng Lhelr levels ln Lhe blood leadlng Lo reduced fasLlng plasma glucose (lC) and posLprandlal
plasma glucose (C) levels ln a glucosedependenL manner MeLformln lmproves glucose Lolerance ln
Lype 2 dlabeLes by decreaslng hepaLlc glucose producLlon and lnLesLlnal absorpLlon of glucose and by
lmprovlng lnsulln senslLlvlLy lL generally does noL cause hypoglycemla
komblglyze O8 has noL been sLudled ln comblnaLlon wlLh lnsulln
||n|ca| tr|a|s A sLudy lnvolvlng LreaLmenLnalve paLlenLs wlLh Lype 2 dlabeLes who had lnadequaLe
glycemlc conLrol on dleL and exerclse was conducLed Lo evaluaLe Lhe safeLy and efflcacy of saxagllpLln +
meLformln lmmedlaLerelease CoadmlnlsLraLlon of saxagllpLln 3 mg/day plus meLformln resulLed ln
slgnlflcanL lmprovemenLs ln hemoglobln (Pb)Ac fasLlng plasma glucose and Lwohour posLprandlal
glucose compared wlLh placebo plus meLformln
ln anoLher sLudy saxagllpLln 23 mg and 3 mg was glven as addon Lherapy Lo paLlenLs wlLh lnadequaLe
glycemlc conLrol on meLformln lmmedlaLerelease alone 1hls comblnaLlon provlded slgnlflcanL
lmprovemenLs ln PbAc lC and C compared wlLh placebo addon Lo meLformln lmmedlaLe
release
Adu|ts 1ake once dally wlLh evenlng meal Swallow whole lndlvlduallze LlLraLe based on response
Maxlmum saxagllpLln 3 mg/day and meLformln exLendedrelease 2000 mg/day ConcomlLanL sLrong
C?3A4/3 lnhlblLors maxlmum saxagllpLln 23 mg/day
h||dren -oL recommended
ontra|nd|cat|ons 8enal lmpalrmenL (serum creaLlnlne 3 mg/dL men 4 mg/dL women)
MeLabollc acldosls dlabeLlc keLoacldosls ConcomlLanL lnLravascular lodlnaLed conLrasL agenLs (suspend
durlng and for 48 hours afLer use)
Jarn|ngs]recaut|ons -oL for LreaLlng Lype dlabeLes Conflrm normal renal funcLlon before sLarLlng
monlLor (especlally ln paLlenLs aged 80 years and older) Avold ln hepaLlc dlsease ulsconLlnue lf lacLlc
acldosls shock acuLe Ml sepsls or hypoxemla occurs Suspend Lherapy lf dehydraLlon occurs or before
surgery MonlLor hepaLlc funcLlon hemaLology (especlally serum vlLamln 82 ln suscepLlble paLlenLs)
Llderly deblllLaLed uncompensaLed sLrenuous exerclse malnourlshed or deflclenL calorlc lnLake
adrenal or plLulLary lnsufflclency or alcohol lnLoxlcaLlon lncreased rlsk of hypoglycemla regnancy
(CaLegory 8) nurslng moLhers noL recommended conslder uslng lnsulln lnsLead
nteract|ons SaxagllpLln poLenLlaLed by sLrong C?3A4/3 lnhlblLors (eg keLoconazole aLazanavlr
clarlLhromycln lndlnavlr lLraconazole nefazodone nelflnavlr rlLonavlr saqulnavlr LellLhromycln)
CaLlonlc drugs ellmlnaLed by renal Lubular secreLlon (eg amllorlde dlgoxln morphlne procalnamlde
qulnldlne qulnlne LrlamLerene LrlmeLhoprlm ranlLldlne vancomycln) may lncrease meLformln levels
Avold excesslve alcohol lnLake (poLenLlaLes effecLs of meLformln on lacLaLe) ulureLlcs sLerolds
phenoLhlazlnes phenyLoln sympaLhomlmeLlcs calclum channel blockers lsonlazld nlacln oLhers may
cause hyperglycemla lncreased rlsk of hypoglycemla wlLh alcohol sulfonylureas beLablockers may
mask hypoglycemla
Adverse react|ons Cl upseL upper resplraLory lnfecLlon urlnary LracL lnfecLlon headache
nasopharynglLls hypersenslLlvlLy reacLlons lacLlc acldosls