Everything you need to know about Dapagliflozin mechanism of action

Dapagliflozin is a newer antidiabetic drug that belongs to the gliflozin class family. This class is also called SGLT2 inhibitors.
Dapagliflozin has a lot of benefits. It not only controls your blood sugar level but also helps to reduce the progression of heart disease and kidney disease.

In this post, we will talk about this potent antidiabetic drug and understand how dapagliflozin’s mechanism of action works in diabetes, heart disease and kidney disease.

Dapagliflozin has a novel and unique mechanism of action.

Mainly, typical antidiabetic drugs increase insulin secretion by working on the pancreas.


On the contrary, this gliflozin drug is not dependent on the beta cells of the pancreas. Dapagliflozin directly works on the kidney and removes the excess glucose from your blood by the kidney via inhibiting the SGLT-2 transporter.

1. Everythingyouneedtoknowabout
Dapagliflozinmechanismofaction
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Introduction
Today,wewilldiscussanovelantidiabeticdrugwhichhasbeenpopularfor
afewyears.Yes,Iamtalkingaboutdapagliflozin.Here,youwilllearnabout
dapagliflozinmechanismofactionsummary,uses,dosage,
contraindications,sideeffects,etc.
Theprevalenceofdiabetesisbeingincreasedthroughouttheworld.Our
researchersarecontinuouslyworkingonitandtryingtofindaninnovative
therapeuticapproachtocontroldiabetes.
Dapagliflozinhasbeenfoundduringresearch.Ithasauniquemechanism
ofactionbecauseitdoesnotrequiretheactionofinsulin.
Itremovesyourelevatedbloodglucosethroughthekidneyviaurine.

2. Dapagliflozinhasalotofbenefits.Itnotonlycontrolsyourbloodsugarlevel
butalsohelpstoreducetheprogressionofheartdiseaseandkidney
disease.
Inthispost,wewilltalkaboutthispotentantidiabeticdrugandunderstand
howdapagliflozin’smechanismofactionworksindiabetes,heartdisease
andkidneydisease.
Let’sgetstartedrightaway.
Whatistheuseofdapagliflozin?
Dapagliflozinisanewerantidiabeticdrugthatbelongstothegliflozinclass
family.ThisclassisalsocalledSGLT2inhibitors.
ThefullformofSGLT2inhibitorsissodium-glucosecotransporter-2
inhibitors.
Therearetwomoredrugsinthisclass,i.e.EmpagliflozinandCanagliflozin.
Dapagliflozinwasapprovedformedicalusein2014bytheUSFDAwith
thebrandnameFarxiga.ItwasdevelopedbyAstraZeneca.
ItwasmarketedinEuropeancountriesunderthebrandnameForxiga.The
currentroleofdapagliflozininfollowingindications–

3. UseofDapagliflozininT2DM
DapagliflozinisthefirstnovelSGLT2inhibitorforthemanagementoftype2
diabetesmellitus.
Thisdrugisconsideredasecond-lineagenttotreatT2DM.Itmaybegiven
asafirst-lineagentifmetforminiscontraindicated.
Dapagliflozinisusedwithdiet,exerciseandotherantidiabeticdrugsto
improveglycemiccontrol.
UseofDapagliflozininHeartDisease
InJuly2020,researchersfoundtheeffectofdapagliflozininNYHAclassII
toIVheartfailure.
Here,NYHAisaNewYorkHeartAssociationthatrepresentsthestagesof
heartfailureinclasses.

4. AccordingtoarecentstudyinAugust2023,ithasbeenshownthat
dapagliflozinsignificantlyreducesall-causemortality,deathfrom
cardiovascularproblems,andhospitalisationduetoheartfailure.
Therefore,dapagliflozincanbeusedasanoff-labelinheartfailurepatients
ifthepatientdoesnothavediabetesmellitus.Butthisdrugcouldbethe
bestchoiceifyouhaveaheartfailurewithdiabetesmellitus.
UseofDapagliflozininkidneydisease
InApril2023,theeffectofdapagliflozinwasfoundtoimprovekidney
outcomesinkidneydisease.
AstudypublishedinKidneyInternationalReportsin2022statedthat
dapagliflozinreducestheriskofend-stagerenaldiseaseinpatientswith
chronickidneydisease,whetherdiabeticornon-diabetic.
Howdoesdapagliflozinworkinthebody?
Dapagliflozinhasanovelanduniquemechanismofaction.
Mainly,typicalantidiabeticdrugsincreaseinsulinsecretionbyworkingon
thepancreas.
Onthecontrary,thisgliflozindrugisnotdependentonthebetacellsofthe
pancreas.Dapagliflozindirectlyworksonthekidneyandremovesthe
excessglucosefromyourbloodbythekidneyviainhibitingtheSGLT-2
transporter.
Let’sunderstandthisdapagliflozinmechanismofactionsummaryindetail
withbasicconcept–

5. Physiology&functionofSGLT-2transporter
Usually,SGLT-2isatransporterorpumpthatispresentinyourPCT
(ProximalConvolutedTubules)ofthekidney’snephron.
SGLT-2standsforsodium-glucosetransportprotein.Theprimaryfunction
ofthistransporteristoreabsorb(orreuptake)sodiumandglucoseintoyour
blood.
Threemainstepsareinvolvedinurineformation:filtration,reabsorption,
andsecretion.
Yourbodyfiltersyourglucoseinthenephron.Then,itreabsorbs90%of
glucoseintoyourbloodbyasodium-glucosepumpandexcretestherestof
thecontent.
DapagliflozinmechanismofactioninT2DM

6. Indiabetes,havingexcessiveglucoseisnotgood.
Wealreadyhavealotofantidiabeticdrugsthatneedtheactionofinsulin.
However,researcherswantedtodosomethingbeyondinsulin,where
insulinisnotrequired.
Therefore,scientistshavemadeanincrediblemoleculethatis
dapagliflozin.
Dapagliflozinworksonthekidney.Thespecialtyofthismoleculeisthatit
restrictsthere-entryofglucoseintoyourblood.
Thisdrugstopstheglucosereabsorptionstepinurineformationby
inhibitingSGLT-2(sodium-glucosetransportprotein-2).
Thisway,thedapagliflozindrugdecreasesyourbloodglucoselevelby
excretingtheglucosecontentviaurine.
That’swhydapaglifloziniscalledSGLT2inhibitor.

7. Dapagliflozinmechanismofactioninheartfailure
Dapagliflozinworksasanosmoticdiuretic.Duetothisosmoticdiuretic
mechanism,dapagliflozinprotectsthecardiovascularandhelpsincardiac
remodelling.
Ifyouhaveheartfailure,dapagliflozinhelpsdecreasetheworkloadonyour
heart.
Thisdrugexcretessodiumfromyourbloodandcreatesahyponatremic
effect.Duetothiseffect,itdecreasesthepreloadandafter-loadeffecton
theheart.Italsoimprovestheejectionfractionofyourheart.
Onceyoustarttakingthisdrug.Youwillbegintofeelimprovementinthe
symptomsofheartfailure,suchasbreathlessness,tirednessandswelling
inyourlowerlegs.
ManystudiessuggestSGLT2inhibitorshavecardiovascularbenefits,such
as–
●AstudypublishedinJournalofEndocrinology,Metabolismand
DiabetesofSouthAfrica2023showsthecardiorenalbenefitsof
SGLT2inhibitorslikeempagliflozin,canagliflozin,anddapagliflozin.
●Areviewandmeta-analysisstudypublishedinESCHeartFailure
2020alsorevealedthebenefitofanSGLT2inhibitorinheartfailure.
●Accordingtoastudyofthecurrentcardiologyreport,2018,SGLT2
inhibitorshelpdecreaseyourbloodpressureandcardiovascularrisk.

8. DapagliflozinmechanismofactioninCKD
CKDstandsforchronickidneydisease,whereapersonstartslosing
nephroncells,whichstopsthekidney’sfunctionovertime.
Itcouldbeduetoglomerulonephritis,type2diabetes,hypertensionor
cardiovasculardisease.
TakingdapagliflozinblockSGLT-2proteinhelpstoreduceinflammationand
pressureinthekidneys.Itprotectsagainstprogressivekidneydamage.
Dapagliflozindecreasestheintraglomerularpressurebynatriuresiseffect
(excretionofsodiumintheurine),whichfurtherhelpstoreduce
albuminuria.
Italsodecreasesinflammatorymediators,suchasinterleukin-6,nuclear
factor-kB,andprofibroticfactors.
Dapagliflozinalsoactsasanephroprotectivedrugwithorwithoutdiabetes.
dapagliflozinmechanismofactionpdf
Whatarethemostcommonsideeffectsofdapagliflozin?
Inadditiontoitstherapeuticeffects,dapagliflozinmayproducesome
unwantedeffectsaswell.
1.FrequentUTI(Urinarytractinfection)
Thediuresiseffectofdapagliflozinmaycausebacterialorfungalinfections
likegenitalmycoticinfections–
●Vulvovaginalcandidiasis(vaginalfungalinfection)
●Balanitis(pain,inflammation,andirritationinthepenis)

9. So,youshouldmaintainpersonalhygiene,especiallyingenitalareas.
2.Dehydration
Youmayhavedehydrationduetoglucosuria/glycosuriaandtheosmotic
diuresiseffectofgliflozin.Youneedtotakeasufficientamountofwaterto
avoiddehydration.
3.Hypotension
Thenatriuresiseffect(lossofsodiumintheurine)ofdapagliflozinmay
decreaseyourbloodpressurelevelandcauseahypotensiveeffect.
So,itisalsoahelpfuldrugifyouhavehypertensionwithtype2diabetes.
Butyouneedtoreducethedoseofyourexistingantihypertensive
medicationslikeACEinhibitors,diureticsorothers.
4.Weightloss
Youwillobserveslightweightreductionduringgliflozintherapybecause
youwillbelosingcalories(orglucose)bytheglucosuriaeffect.However,it
maybebeneficialforobesepatients.
5.Hypoglycemia
Dapagliflozinmaycausemildhypoglycemiaifitisusedincombinationwith
insulininjectionorsulphonylurea-likedrugs.
Itwouldhelpifyoureducethedoseofinsulinorotheroralhypoglycaemic
agentswhiletakingSGLT2inhibitordrugs.

10. 6.Polyuriaandpolydipsia
Youmayhaveanexcessivethirstandfrequenturinationduetotheosmotic
diureticeffectofdapagliflozin.
7.Riskofbladdercancer
Asweknow,urinarytractinfection(UTI)isdapagliflozin’smostcommon
sideeffect.ThisUTImayfurthercontributetobladdercancer.
Whennottousedapagliflozin?
Dapaglifloziniscontraindicatedincertainconditions–
1.Pregnancyandbreastfeeding
DapagliflozincomesincategoryCmedications.
Currently,nodataareavailableontheuseofdapagliflozininpregnant
women.Theresearcherfoundreproductivetoxicityinanimalsduring
dapagliflozin,especiallyin2ndand3rdtrimesters.
Itwasalsofoundthatdapagliflozincanbesecretedinmilkwhile
breastfeeding.
Therefore,itwouldbebesttoavoiddapagliflozininpregnancyand
lactation.Wealreadyhaveinsulininjectionsandmetformintabletsasa
saferoption.

11. 2.Severekidneydisease(GFR<30ml/min)
Dapagliflozindrugshouldnotbeusedforseverekidneydamage,
especiallyinstages4and5ofCKD.
Atthesestages,theGFR(GlomerularFiltrationRate)valuedecreases
below30ml/min.
ThisdrugisnotrecommendedinGFR30to40ml/min.Youshouldstrictly
avoiddapagliflozinifsomeonehasaGFRvalueoflessthan30ml/min.
3.Historyofbladdercancer
Youneedtoavoiddapagliflozinifapatienthasactivebladdercancerora
historyofbladdercancer.
4.Historyofketoacidosis
Youshouldavoidthisdrugifyouhavehadketoacidosisinthepast
becauseSGLT-2inhibitorsthemselvescauseketoacidosis.
InFeb2022,astudyreviewedthedapagliflozinisassociatedwithdiabetic
ketoacidosis.
Inthiscondition,yourbodystartstoproduceketonebodies.Duetothis,
yourbloodbecomesacidic(pHbelow7).
Inketoacidosis,youmayfeelburningwhileurinating,bloodinurine,painin
thelowerabdomen,andshortnessofbreath.Ifyouobservethese
symptoms,youshouldstopthismedicineimmediatelyandcontactyour
doctor.
5.Allergicreaction

12. Youshouldimmediatelydiscontinuethismedicineifyoufeela
hypersensitivereactiontothisdapagliflozin.
Howandwhentotakedapagliflozin?
Dapagliflozincausespolyuriaduetoitsosmoticdiureticeffect.So,taking
onetabletinthemorningwithorwithoutamealisalwaysbetter.
Thedoseofdapagliflozindependsontheseverityofthediseaseandtype
ofdisease,suchas–
Dapagliflozindosefortype2diabetesmellitus
Dapagliflozinisconsideredafirst-lineagentifmetforminiscontraindicated.
Youmaybeprescribedthismedicineatthedisease’sinitialorlatestage.It
canbeusedasamonotherapyoraddedtoinsulin/anotheroral
hypoglycemicagent.
ThestartingdoseofdapagliflozininT2DMis5mg,administeredonce
daily.Itcanbeincreasedupto10mgifclinicallyindicated.
Themaximumdapagliflozindoseperdayis10mg.
Dapagliflozindoseforheartdisease
Therecommendeddoseofdapagliflozinis10mgoncedailydosingin
NYHAclassII–IVheartdisease.
Dapagliflozindoseforchronickidneydisease

13. Theusualdoseofdapagliflozinis10mgoncedailyinchronickidney
disease.
TakingdapagliflozinincreasesserumcreatinineandreduceseGFR.These
changesmaybemoreprevalentinelderlypatientsandpatientswith
impairedrenalfunction.
So,itwouldhelpifyoukeptinmindGFRvalues.ThenormaleGFRvalue
is90ml/minormore.
Nodose
adjustment
Not
recommended
Contraindicated
eGFRvalues
(ml/min/1.73m2)
45orabove30orlessthan
45
Lessthan30
WhatdapagliflozinbrandsarepopularinIndia?
DapagliflozinisprominentinIndiawithbrandnamesof–
●Forxiga5mgor10mgtablet
●Oxra5mgor10mgtablet
●Dapaone5mgor10mgtablet
●Sugaflo5mgor10mgtablet

14. Dapagliflozinisalsoavailableincombinationwithtraditionalantidiabetic
drugslike–
1.Dapagliflozinandmetformincombination
YoucangetthisfixeddosecombinationofDapagliflozin&MetforminHCL
extended-releasetabletswithbrandnamesof–
●GledepametXR10/500mgor1000mg
●GlucretaM5/500or10/1000
●DapaturnM5or10mgtabletER

15. ●DapanormM5/500mg
2.Dapagliflozinandvildagliptincombination
TheFDCofdapagliflozin&vildagliptinsustainreleasetabletisavailable
withbrandnamesof–
●Jalra-DP10mg/100mg
●DaparylV10mg/100mg
●TorglipD10mg/100mg
●ZukanormD10mg/100mg
3.Dapagliflozin+vildagliptin+metformincombination
ThistripleFDCcombination(Dapagliflozin+vildagliptin+metformin)is
availablewithbrandnamesof–
●DaparylVM10mg/500mg/100mgTablet
●Zomelis-DMForteTabletSR
●JalraTrioTablet
●Vylda-DM100/10/1000TabletSR
Whataretheclinicalbenefitsofdapagliflozin?

16. Dapagliflozindoesnotonlyimproveyourglycaemiccontrol,butitalsohas
manybenefitslike–
●Effectiveinheartfailure(NYHAclassII-IV)
●EffectiveinchronickidneydiseaseifGFRis45mg/mlorabove
●Rarelycausehypoglycaemia
●Helpstoreducebloodpressure
●Helpsinweightreduction
●Reducefattylivercontent,especiallyNAFLD
Conclusion
Dapagliflozinisapotent,welltoleratedandsafestantidiabeticdrug.
Inthispost,weunderstoodthedapagliflozinmechanismofactionandhow
itworksindiabetes.
Besidesitsuseindiabetes,dapagliflozinhasacardio-renaleffect.
Thismedicinecanbeconsideredarisingstarintreatingdiabetespatients.
Thiswasallaboutthedapagliflozinmechanismofactionsummary,uses,
benefits,sideeffects,andcontraindications.
Pleasesharethispostonsocialmediaifyoufounditinformative.
FAQ

17. Q1.Isdapagliflozinbadforthekidneys?
Dapagliflozinwouldbetherightchoiceforkidneydisease,whoseGFR
valueismorethan45ml/min.ItcanbecontraindicatedifGFRislessthan
30ml/min.
Q2.Doesdapagliflozinincreasecreatinine?
DapagliflozindrugincreasesserumcreatininelevelsandreduceseGFR.
Youshouldavoidthismedicineifyouhaveahighercreatininelevelor
lowerGFRvalue.
Q3.Howlongdoesdapagliflozintaketowork?
Theonsetofactionofdapagliflozinis2hours.Yourbloodglucoselevels
willdropafterabouttwohoursoftakingdapagliflozin.However,itmaytake
uptoaweektobecomefullyeffective.
Q4.Whichisbetter,metforminordapagliflozin?
Metforminisafirst-lineantidiabeticdrug.Supposemetforminis
contraindicatedorineffective.Inthatcase,dapagliflozinmaybea
second-lineoptionforthetreatmentofdiabetes.
Q5.Whatisasubstitutefordapagliflozin?
Ifdapaglifloziniscontraindicatedornottolerated.Then,youmaygoto
otherdrugsofthisclass,suchasCanagliflozinorEmpagliflozin.
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