Antidiabetic drug classification_pdf.pdf

Antidiabetic drugs are those drugs that reduce blood sugar levels by releasing insulin or overcoming insulin resistance.

Antidiabetic drugs have been classified into two forms: injectable and oral antidiabetic drugs (OHA – Oral Hypoglycemic Agents)

- Injectable Diabetes Medications

Injections are not the first choice drug for diabetes. They are last-line medication options if your diabetes is getting uncontrolled. You can be given the following injections –
*Insulin analogues
*Incretins based drugs such as GLP-1 analogs (Exenatide and Liraglutide)

-Oral Hypoglycemic Drugs (or Antidiabetic Agents)

The major drawback of insulin analogues is that it is given by injection. That’s why oral hypoglycaemic medicines are preferable and commonly used in type-2 diabetes mellitus treatment.
Oral hypoglycemic agents are quite effective to control your high blood glucose levels. It only works on type 2 diabetes mellitus.
Currently, there are 4 ways/groups of oral antidiabetic medicines to reduce high blood sugar levels –

*Insulin sensitizers
*Insulin secretagogues
*Decrease intestinal absorption of glucose
*Excretion of glucose from urine

Oral antidiabetic medications have been classified into 7 classes, such as –
1. Biguanides
2. Thiazolidinediones
3. Sulfonylureas
4. Meglitinides
5. DPP-4 inhibitors
6. Alpha-glucosidase inhibitors
7. SGLT2 Inhibitors

This article will explore various antidiabetic drug classifications, their mechanism of action, uses, side effects and dosage.
Moreover, we will understand what medicines are preferable and suitable for treating diabetes mellitus.

1. AntidiabeticDrugClassificationand
MechanismofAction:algorithmfor
managementofdiabetesmellitus
PostedBySUMITSHARMA
Contents
●Introduction
●Whatareantidiabeticdrugs?
●Whataretheclassificationsofantidiabeticdrugswithexamples?
InjectableDiabetesMedications
OralHypoglycemicDrugs(orAntidiabeticAgents)
●WhichdrugsareBiguanides?

2. Mechanismofactionofmetformin
Sideeffectsofmetformin
Dosageofmetformin
●WhatdrugsareSulphonylureas?WhatcanbetheroleofSulphonylureasintreatmentofdiabetes?
Sulfonylureasmechanismofaction
SideeffectofSulphonylureas
DosageofSulphonylureas
●Whatareexamplesofmeglitinideanalogues?Whymeglitinidesarebetterthansulfonylureas?
Meglitinide’smechanismofaction
BenefitsofMeglitinides
DosageofMeglitinides
●Whatisthemechanismofthiazolidinediones?Ispioglitazonesafetotakefordiabetes?
Pioglitazonemechanismofaction
Pioglitazonesideeffectsandcontraindications
Pioglitazonebenefits
●WhichdrugsareDPP-4inhibitors?HowdoDPP-4inhibitorswork?

3. DPP-4inhibitor’smechanismofaction
DPP-4inhibitorsbrandnames
●Whatarecurrentlyusedalpha-glucosidaseinhibitors?Whatistheclinicalroleofthesedrugsin
diabetesmellitus?
Alpha-glucosidaseinhibitor’smechanismofaction
Alpha-glucosidaseinhibitor’ssideeffects
Acarboseandvoglibosedosage
●WhatarethemostcommonSGLT2inhibitors?HowdoSGLT2inhibitorswork?
SGLT2inhibitor’smechanismofaction
SGLT2inhibitor’ssideeffects
●Whatareinsulinanalogues?Whatarethedifferenttypesofinsulinnames?
1.Short-actinginsulin
2.Ultrashort-actinginsulin
3.Intermediate-actingInsulin
4.Long-actinginsulin
5.Ultra-longactinginsulin

4. 6.PremixedInsulin
Combinationofintermediateandultra-short-actinginsulin
Combinationofintermediateandshort-actinginsulin
Combinationofultra-shortandultra-long-actinginsulin
●Whatistheroleofliraglutideandexenatideindiabetesmellitus?
●Whatisthepharmacologicalmanagementofdiabetesmellitus?
STEP1–Mono-therapy
STEP2–Dualtherapy
STEP3–TripleTherapy
STEP4–Injectablewithcombinations
●Conclusion
●FAQ
Q1.Whatisthefirstdrugofchoicefordiabetes?
Q2.Whichantidiabeticdrugclassleadtoglycosuria?
Q3.Whatisthenewdrugfordiabetes?
Q4.Isrepaglinidesafeforkidneys?

5. Q5.Islinagliptinsafeforkidneys?
Introduction
Youmusthaveadiabeticpersoninyourfamilyorrelatives.Theywouldbetaking
differentdiabetesmedications.Today,wewillgettoknowthecomplete
antidiabeticdrugclassification.
Lifestylemodifications(suchasdietcontrolandexercise)arethegoldstandardfor
treatingdiabetes.
Weshouldaddthebestdiabeticdietplan,suchaslowglycemicindexfoods,low
glycemicloadfoods,highproteinfood,properfluidintake,etc.
Supposethelifestylechangesdonotworkandyourbloodsugarisstillhigh.Inthat
case,antidiabeticdrugsshouldbeaddedtoyourdiabetestreatment.
Itdoesnotmeanyoushouldstopexercisingandnoteatinghealthyfoods.Youhave
toaddonmedicinewithhealthylifestyleactivities.
Thisarticlewillexplorevariousantidiabeticdrugclassifications,theirmechanism
ofaction,uses,sideeffectsanddosage.
Moreover,wewillunderstandwhatmedicinesarepreferableandsuitablefor
treatingdiabetesmellitus.
Letthearticlebestarted.
Whatareantidiabeticdrugs?
Antidiabeticdrugsarethosedrugsthatreducebloodsugarlevelsbyreleasing
insulinorovercominginsulinresistance.Itmakesyourbloodsugarlevelinnormal
ranges–
●FBS=99mg/dlorbelow

6. ●PPBS=140mg/dlorbelow
●RBS=below200mg/dl
●HbA1C=<5.7%
Thesedrugsresolvediabeticsymptomsbydecreasingbloodsugarlevels,suchas–
●Decreasetiredness
●Controlexcessiveurination
●Controlexcessiveeating
●Controlintensethirst
●Preventweightloss
●Stopdehydration
Antidiabeticdrugsalsopreventdiabeticcomplicationssuchas
●Macrovascularcomplications–ReducetheriskofCerebrovascularDisease
(CVD),Coronaryarterydisease(CAD),Peripheralvasculardisease(PVD),
andRenovascularDisease(RVD)
●Microvascularcomplications–ReducetheriskofDiabeticneuropathy,
Diabeticnephropathy,andDiabeticretinopathy

7. Whataretheclassificationsofantidiabeticdrugswith
examples?
Antidiabeticdrugshavebeenclassifiedintotwoforms:injectableandoral
antidiabeticdrugs(OHA–OralHypoglycemicAgents)
InjectableDiabetesMedications
Injectionsarenotthefirstchoicedrugfordiabetes.Theyarelast-linemedication
optionsifyourdiabetesisgettinguncontrolled.Youcanbegiventhefollowing
injections–
●Insulinanalogues
●IncretinsbaseddrugssuchasGLP-1analogs(ExenatideandLiraglutide)
OralHypoglycemicDrugs(orAntidiabeticAgents)
Themajordrawbackofinsulinanaloguesisthatitisgivenbyinjection.That’swhy
oralhypoglycaemicmedicinesarepreferableandcommonlyusedintype-2
diabetesmellitustreatment.
Oralhypoglycemicagentsarequiteeffectivetocontrolyourhighbloodglucose
levels.Itonlyworksontype2diabetesmellitus.
Currently,thereare4ways/groupsoforalantidiabeticmedicinestoreducehigh
bloodsugarlevels–
●Insulinsensitizers
●Insulinsecretagogues

8. ●Decreaseintestinalabsorptionofglucose
●Excretionofglucosefromurine
Oralantidiabeticmedicationshavebeenclassifiedinto7classes,suchas–
1.Biguanides
2.Thiazolidinediones
3.Sulfonylureas
4.Meglitinides
5.DPP-4inhibitors
6.Alpha-glucosidaseinhibitors
7.SGLT2Inhibitors
Groups Classes Examplesofmedicines
Insulinsensitizers
Biguanides Metformin
ThiazolidinedionesPioglitazone
Sulfonylureas Glipizide,Glimepiride,
Glyclazide,

9. Insulinsecretagogues
Glyburide
Meglitinides Repaglinide,Nateglinide
DPP-4inhibitorsSitagliptin,
Saxagliptin,
Linagliptin,
Vildagliptin
Decreaseintestinal
absorptionofglucose
Alpha-glucosidase
inhibitors
Acarbose,Voglibose
Miglitol
Excretionofglucose
fromurine
SGLT2InhibitorsDapagliflozin,
Empagliflozin,
Canagliflozin

10. WhichdrugsareBiguanides?
Metforminisadrugthatbelongstothebiguanidecategory.
Everyoneknowsthisdrugbecausemetformintabletisthemostcommonly
prescribedmedicinefortype2diabetesmellitus(T2DM).Thisistheinitialdrug
wherediabetestreatmentshouldbestarted.
Itisconsideredafirst-linedrugintreatingtype2diabetesmellitus.
Let’sknowthepharmacologyofmetformindrug–
Mechanismofactionofmetformin
Metformindrugworksinthreeways–

11. ●Decreaseglucoseabsorptionfromtheintestine
Metforminreducesgluconeogenesis.Thismeansitdecreasestheabsorptionor
formationofanewglucosemolecule(e.g.,protein)fromtheintestine.
●Decreaseglucoseproductionintheliver
Metforminreduceshepaticglycogenolysis.Thismeansthatitdecreasesthe
breakdownofglycogen,whichconvertsintoglucoseanddecreasesglucose
transportfromthelivertotheblood.
●Increaseinsulinsensitivityandglucoseuptakeincells
Metforminhelpstoreduceinsulinresistance.ThisdrugactivatesInsulin,which
helpstotransportglucosemoleculesfrombloodtocells.

12. Sideeffectsofmetformin
Themainsideeffectsofmetforminarerelatedtothegastrointestinaltract,whichis
verycommon.Thismedicinecancausediarrhoea,bloating,flatulence,nausea,etc.
Youmighthavedangeroussideeffectsifyouareusingmetformin.Lacticacidosis
hasbeenreportedduetotheuseofexcessivemetformindoses.
Thissideeffectcouldbefatalifyourkidneyandliverarecompromised.
MetformincanalsocausevitaminB12deficiency.Youmayneedtoaddvitamin
B12supplementsalongwithmetformin.
Dosageofmetformin
Themaximumdosageofmetforminperdayis2000mg.Itwouldbebestifyoudo
notgobeyondthisdose.
Initially,yourdiabetestreatmentshouldbestartedat500mgtwicedaily.Itcould
beincreasedupto1000mgtwiceifdiabetesisuncontrolled.
Thisdrugcanbecombinedwithotherantidiabeticclasseslikesulphonylureas,
DPP-4inhibitors,SGLT2inhibitors,Meglitinides,thiazolidinediones,and
alpha-glucosidaseinhibitors.
Youcantakemetforminjustafterhavingyourmeal.

14. WhatdrugsareSulphonylureas?Whatcanbetheroleof
Sulphonylureasintreatmentofdiabetes?
Youmusthaveheardthenamesofdiabeticmedicineswhichbeginwith“Gli”,like
Glimepride,Gliclazide,Glibenclamide,andGlipizide.

15. Thesedrugsaresecond-generationofsulphonylureas.Thefirstgenerationof
sulphonylureas,suchastolbutamideandchlorpropamide,arerarelyused.
ThesulphonylureashaveacrucialroleinthetreatmentofT2DMbyreleasing
insulinfromthepancreas.
ThesedrugsarealsoknownasInsulinSecretagogous.
Supposeyouareintolerantofmetformin.Inthatcase,youcanusesulphonylureas
alone.
Itcanalsobeusedincombinationwithmetformin.
Sulfonylureasmechanismofaction
Whenyoutakeanysulphonylureasdrug.Theygotoyourpancreasandstimulate
betacells.
Here,itblockstheATP-sensitivepotassium(K+)channel.Duetothis,ahigh
concentrationofpotassiuminyourbetacellsstimulatesthecalciumchannel.
Assoonasthecalciumchannelopens,itstartslettingtheinfluxofcalciumions.
Thisincreasedinfluxofcalciumionspenetratesthelarge,densecorevesicles
whereinsulinisstored.
Inthisprocessofdepolarisation,exocytosistakesplace,andinsulinissecreted.
Overall,sulphonylureashelptosecreteinsulin.That’swhyitiscalledInsulin
Secretagogues.
Afterreleasinginsulin,itgoestotheliverbythehepaticportalvein.Eventually,
insulinreachesthecentralbloodcirculation.
Here,insulingoestocellsandbindstotheTyrosineKinasereceptor.Afterthat,it
letstheglucosecomeinsidecellsbyGLUT-4transporters.

16. SideeffectofSulphonylureas
Youmayhavehypoglycaemiaandweightgain-likesideeffectsduring
sulphonylureastherapy.
Hypoglycemiawasverycommoninfirst-generationsulphonylureaslike
tolbutamideandchlorpropamide.
Theriskofhypoglycaemiaislowerinnewersulphonylureasdrugslikeglimeride,
gliclazide,etc.
DosageofSulphonylureas
Itisusuallyrecommendedtostartwithalowdose,suchasglibenclamide2.5mg,
glimepiride2mg,gliclazide30mg,etc.

17. Thedoseofsulphonylureascanbeincreasedeverytwoweeksifyourglycemic
patternisnotcontrolledwell.
Itwouldbebestifyoutakesulphonylureas30minbeforeeachmealonceortwice
adayasneeded.

18. Whatareexamplesofmeglitinideanalogues?Why
meglitinidesarebetterthansulfonylureas?
Meglitinidesarealsoeffectiveoralhypoglycaemicdrugs.Therearetwomedicines
inthiscategory,suchasrepaglinideandnateglinide.

19. Repaglinideisconsideredasuperiorandpreferabledrugbecauseofbetter
glycemiccontrol.Iteffectivelycontrolselevatedpost-prandialbloodsugar(PPBS)
inT2DM.
ThesedrugshaveagoodreductioninHbA1C,around0.2to1.5%.
Accordingtocurrentguidelines,meglitinidesarenotrecommendedaspartofan
oraldiabetestreatmentregimen.Still,theymaybeusedinsteadofsulfonylureasin
selectedpatients.
Meglitinidescanbeusedifsomeonehasanallergyorisintolerantof
sulphonylureas.ItcanalsobeusedinkidneydiseasepatientswhohaveT2DM.
Meglitinide’smechanismofaction
MeglitidineshavesimilarmechanismstoSulphonylureas.Theyblockthe
potassiumchannelandsecreteinsulin.ThesemedicinesarealsoknownasInsulin
Secretagogues.
BenefitsofMeglitinides
●Repaglinideisthesafestandmostwell-tolerateddruginchronickidney
disease.
●Asafeandeffectivedruginanelderlydiabeticpatient
●Well-controlledpost-prandialbloodglucose(PPBG)level
●Quicklyabsorbedinthebloodstream
●Fastonsetofaction

20. ●Lowerriskofhypoglycaemia
DosageofMeglitinides
Thisclassofmedicinesshouldbetaken10minutesbeforeeachmealtocontrol
yourPPBSlevel.
Therecommendeddoserangeofrepaglinideis0.5mgto4mg.Itcanbeincreased
upto16mgasneeded.
Whatisthemechanismofthiazolidinediones?Is
pioglitazonesafetotakefordiabetes?
Thiazolidinediones(TZDs)arealsoknownas“Glitazones”.Glitazonesarethe
secondorthird-linetreatmentoptionfortype2diabetesmellitus.Itincludes
rosiglitazoneandpioglitazone.
In2010,Rosiglitazonewasbannedinmanycountriesduetoincreasing
life-threateningriskssuchasmyocardialinfarction,CHF,strokeanddeath.
ThesedrugshavebeencompletelywithdrawnfromEuropeancountrieslike
GermanyandFranceduetoincreasedriskofbladdercancerandcardiovascular
problems.
Currently,onlypioglitazoneisavailableinsomecountrieslikeIndia.Itisusedasa
mono-therapyincaseofintoleranceofmetformin.
Ifdiabetesisuncontrolled,thencombinationscanbeusedofpioglitazonewith
otherantidiabeticdrugs–

21. ●Dualtherapy(Pioglitazone+Metformin,orSulphonylureas,orDPP-4
inhibitors)
●Tripletherapy(Metformin+Pioglitazone+SGLT2inhibitors)or
(Metformin+Sulfonylurea+Pioglitazone)
Pioglitazonemechanismofaction
Pioglitazonedrugworksonthenuclearreceptor,whichstimulatesPPAR-γ
(peroxisomeproliferator-activatedreceptorgamma).
PPAR-γreceptorsaremainlypresentinfatcells.Italtersthetranscriptionof
severalgenesandenhancesGLUT4expression,improvingglucoseentryintofat
cells.
Overall,itreducesinsulinresistancebyincreasinginsulinsensitivity.

22. Pioglitazonesideeffectsandcontraindications
Themostcommonsideeffectsofpioglitazonearefluidretentionandweightgain.
Youmaynoticeswellinginyouranklesifyouareonpioglitazone.
Youshouldavoidpioglitazoneifyouhaveahistoryofheartdiseasebecauseitmay
worsentheconditionofCHF(CongestiveHeartFailure).
Theliverdysfunctionshavebeenreportedbypioglitazone.So,youmayrequire
monitoringofLFT(Liverfunctiontest).
Accordingtoastudy,pioglitazoneisalsoassociatedwithanincreasedriskofbone
fractures,especiallyinolderwomen.
Pioglitazonehaslackofsafetydatainpregnancy.So,youshouldavoidthisdrug
duringpregnancy.

23. Pioglitazonebenefits
Pioglitazoneeffectivelycontrolselevatedbloodsugarlevelsifthereisaclearcase
ofinsulinresistance.Let’sknowit’scrucialbenefits–
●Well-tolerateddruginT2DM
●DecreaseTG(triglyceride)level
●IncreaseHDLlevel
●Lesshypoglycaemicepisodes
WhichdrugsareDPP-4inhibitors?HowdoDPP-4
inhibitorswork?
DPP-4inhibitorsareconsiderednewerantidiabeticdrugs.Thesedrugsarealso
called“Gliptins”becausethesedrugsendwiththe“gliptins”word.Forexamples–
●Sitagliptin
●Saxagliptin
●Linagliptin
●Vildagliptin
●Teneligliptin

24. Ifmetforminisintolerant,yourdoctorcanstartDPP4inhibitorsasamono-therapy
(singledrugtherapy).
Incasediabetesisuncontrolled,thencombinationscanbeusedofDPP-4inhibitors
withotherantidiabeticdrugs–
●Dualtherapy(DPP4inhibitors+metformin,orsulphonylureas,or
pioglitazone)
●Tripletherapy(Metformin+Sulfonylurea+DPP4inhibitors)
DPP-4inhibitor’smechanismofaction
TakingfoodstimulatesincretinslikeGIP(gastricinhibitorypolypeptide)and
GLP-1(glucagon‐likepeptide‐1).
Theseincretinsgotothepancreasandgettheinsulinsecreted.
But,youmighthaveaproblemwhenDPP-4(Dipeptidyl-peptidase4)enzymesare
released.TheseDPP-4enzymesinhibitthereleaseofincretinsandstopinsulin
secretion.
That’swhyresearchershavemadeamoleculethatinhibitstheDPP-4enzyme.
TheylaunchedDPP-4inhibitors.Thesedrugsarealsoinsulinsecretagogous.
DPP-4inhibitorsarethosedrugsthatinhibitDipeptidyl-peptidase4enzymeand
releaseincretinslikeGIPandGLP-1.Theseincretinshelptoreleaseinsulinto
controlhighbloodglucoselevels.

25. DPP-4inhibitorsbrandnames
TherearesomepopularbrandnamesforDPP-4inhibitordrugs–
●Sitagliptin(Januvia)
●Saxagliptin(Onglyza)
●Linagliptin(Trajenta)
●Vildagliptin(Galvus)

28. Gliptinsarecommonlyusedinfixed-dosecombinationswithmetformindrugslike
–
●Janumet(Sitagliptin50mgandmetforminhydrochloride500mg/1gm)
●KombiglyzeXR(saxagliptin5mgandmetforminHCl500mg/1gm
extended-release)
●TrajentaDuo(Linagliptin2.5mgandmetforminhydrochloride500mg)
●GalvusMet(VildagliptinandmetforminHCL500mg/1gm)

30. Whatarecurrentlyusedalpha-glucosidaseinhibitors?
Whatistheclinicalroleofthesedrugsindiabetes
mellitus?
Currently,AcarboseandVoglibosearetheclassicalalpha-glucosidaseinhibitors
usedtotreatT2DM.
Supposeyouarenewlydiagnosedwithtype2diabetesmellitus.And,your
post-prandialbloodglucoseisnotcontrolledwithdietorexercise.Inthatcase,this
drugcanalsobeusedasafirst-linedrug.
Itcanalsobeusedwithmetforminandotherantidiabeticdrugs.
Alpha-glucosidaseinhibitor’smechanismofaction

31. Typically,Alpha-glucosidaseisanenzymeinourintestinalbrushborder.
Thisenzymeisreleasedfromthesmallintestinewhenweeatcarbohydrates.It
helpstobreakdowncarbohydratesinthesimplestform,likeglucose.
Indiabetesconditions,thisalpha-glucosidaseenzymeincreasestheprocessof
glucosedigestionandabsorption.Thisisnotgoodinhyperglycaemicstates.
Here,alpha-glucosidaseinhibitors(suchasacarboseandvoglibose)inhibitthe
alpha-glucosidaseenzyme.Itdelaystheprocessofdigestionandabsorptionof
carbohydrates.
Eventually,thesedrugsdecreaseglucoseabsorptioninthebloodstreamandreduce
bloodglucoselevels.
Alpha-glucosidaseinhibitor’ssideeffects

32. Theunabsorbedcarbohydratesmaycauseabdominalbloating,cramping,increased
flatulence,ordiarrhoea.
Youmayhavethesesideeffectsifyouareonvogliboseoracarbose.
Acarboseandvoglibosedosage
Youmaytakeacarbose50to100mgorvoglibose0.2to0.3mgthriceadaybefore
thebeginningofeachmeal.
WhatarethemostcommonSGLT2inhibitors?Howdo
SGLT2inhibitorswork?
SGLT2inhibitorsarenewerantidiabeticdrugsthathelptotreattype2diabetes
mellitus.
TheyarealsoknownasGliflozinsbecausethesemedicinesendwith“gliflozin”,
wordsuchas

33. ●Dapagliflozin
●Empagliflozin
●Canagliflozin
Thisdrugclasscanbeusedasamono-therapyifmetforminisintolerantor
contraindicated.
Incaseofuncontrolledglycemicpattern,itshouldbestartedincombinationsasa–
●Dualtherapy(SGLT2inhibitors+metformin,orsulphonylureas)
●Tripletherapy(Metformin+Sulfonylurea+SGLT2inhibitors)or
(Metformin+Pioglitazone+SGLT2inhibitors)
SGLT2inhibitor’smechanismofaction
SGLT2inhibitorshaveanovelanduniquemechanismofaction.
Inahealthyperson,thereareSGLT-2co-transportersorpumpsintheirkidney’s
nephron.ThefullformofSGLTisSodiumGlucoseCo-Transporter.
Thesetransportersactassymportersthatreabsorbsodiumandglucoseinyour
bloodduringurineformation.
Indiabetesmellitus,re-absorptionofglucoseandsodiumisnotgood,whichmay
worsenyourdiabeticcondition.
Here,SGLT2inhibitorsinhibittheSGLT2co-transportersthatexcretethesodium
andglucosethroughurine.
Duetothisuniquemechanism,itsignificantlyreducesbloodglucoselevels.

34. SGLT2inhibitor’ssideeffects
Youmayhavethefollowingsideeffectsduringgliflozinstherapy–
●Frequenturination
●Dehydrationandhypotension
●Weightloss
●Hypoglycemia
●Excessivethirstandfrequenturination
●Riskoffootamputations

35. ●Riskofbonefractures

36. Whatareinsulinanalogues?Whatarethedifferenttypes
ofinsulinnames?
Insulinshotsarethelast-linemedicationoptiontocontrolhighbloodsugarlevels.
InsulininjectionsareusedtomanagementofType1(T1DM)andType2Diabetes
Mellitus(T2DM).
Ifyoudon’thaveenoughnaturalinsulin,syntheticinsulinshouldbegiventoyou.

37. ThissyntheticinsuliniscalledInsulinanalogue.
Insulinanalogueimitatesthebody’sstandardinsulinreleasepatterns.
Insulinanalogueinjectionsaremadeusingthepancreasofpigs(pork)andcows
(beef).TheycanalsobepreparedbyrecombinantDNAtechnology.
InrecombinantDNAtechnology,scientistsusehumanpancreaticgenesinE.coli
(Escherichiacoli)bacteria.Theymakeinsulinanalogue.
Therearedifferentinsulintypesfordiabetes.Someinsulinanaloguescontrolthe
peakofglucoseconcentration;thatinsuliniscalledBolusInsulin.
Bolusinsulinisfast-actinginsulinthatimmediatelyreleasesinyourbloodstream
andcontrolshighbloodsugarlevels.Theyaregivenimmediatelyjustbeforeyour
meal.
Conversely,thoseinsulinanaloguesthatmaintainyourbloodsugarlevelforalong
timearecalledBasalInsulin.
BasalInsulinisslow-actingorlong-actinginsulin.Theyreleaseslowlyinyour
bloodstream.Whenyoutakebasalinsulin,yourbloodglucoselevelremainssteady
throughoutthedayandnight.
Let’sknowthedifferenttypesofinsulinpreparations–
1.Short-actinginsulin
RegularInsulinorsolubleInsulinisanexampleofshort-actinginsulin.Thisisa
typeofBolusInsulin.ThisinsulinpreparationisinHumanActrapidInjectionat40
IU/ml.
Ifyouseethecartridgeorvialofshort-actinginsulin,itwouldbeaclear
appearance.
Theonsetofactionis30mins,andthedurationis6to8hoursofregularinsulin.

38. Thismeansthatregularinsulintakes30minstoreachyourbloodcirculationafter
subcutaneousinjectionandremainsinyourbloodfor6to8hours.
Itshowsthemaximumeffect(peak)in2to3hours.
YouneedtotakeRegularInsulin30minutesbeforeameal.
ThisisthelimitationofShort-actingInsulin.Itisnotalwayspossibletoinject
insulinbefore30-minutemeal.Itreducespatientcomplianceanddoesnot
significantlyreducePPBGlevels.
Otherinsulinpreparationshavebeendesignedtoovercomethisproblem,suchas
ultra-short,intermediate,long,andultra-long-actingInsulinInjections.
2.Ultrashort-actinginsulin
Themostcommontypeofinsulininjectionisultra-short-actinginsulin.This
injectionreducesthelimitationofRegularInsulin(orShort-actinginsulin).
Itisaclearappearance.
Itquicklyabsorbsinyourbloodstreamwithin5to15mins(onsetofaction).The
durationofactionis2to4hours.
Youneedtoprepareyourmealandtakeashotofultra-short-actinginsulin.Itisan
effectivebolusinsulinbecauseitsignificantlyreduceselevatedbloodglucoselevel
spikesorPPBG.
Examplesofultra-short-actingInsulinareLispro,AspartandGlulisine.Youmight
haveseen–
●InsulinLisproinHumalog100.
●InsulinAspartinNovoRapidandNovoLog
●InsulinGlulisineinApidraSolostar

40. 3.Intermediate-actingInsulin
Intermediate-actinginsulinisaBasalInsulinthatkeepsyourbloodsugarlevel
stablewhenfasting,suchaswhileyousleep.
AnexampleofintermediateInsulinisIsophane.ItisalsoknownasNPH(Neutral
ProtamineHagedorn)Insulin.
Isophaneismainlyusedtomakepremixedinsulin.Itiscompatibletomixwith
shortorrapidshort-actinginsulin.
Youcaneasilyidentifythistypeofinsulin.Whenyouseethevialorcartridgeof
intermediate-actinginsulin,itwouldhaveacloudyappearance.
Theonsetofactionis60to90min.Itwillreachamaximumconcentrationorpeak
in8to10hours.Itwillremaininyourbodyfor20to24hours.

41. YoumightneedtoinjectIsophaneinsulinsubcutaneously(s.c.)onceortwicedaily.
IsophaneorNPHisavailableinthemarketwithHuminsulinandHumulinNbrand
names.
4.Long-actinginsulin
Itisalong-actingbasalinsulinanalogue.Exampleoflong-actingInsulinisInsulin
DetemirandInsulinGlargine.
InsulinglargineisverypopularwiththebrandnamesLantusandBasalog,and
insulindetemirisavailableintheLevemirbrandname.
Theselong-actinginsulininjectionsmaintainyourbloodsugarlevelthroughoutthe
night.Theseinjectionsstarttoworkafter2hrs.
Thedurationofactionis24hrs.Itcanbeinjectedatanytime,butyoushouldtake
itatthesametimeeveryday.
Thelong-actingInsulin(Lantus)isgenerallyrecommendedatbedtime.

42. 5.Ultra-longactinginsulin
Insulindegludecisanultra-long-actingbasalinsulinanaloguethatpreventsstrong
fluctuationofbloodsugarlevels.ItisverypopularwiththebrandnameofTresiba.
ThedurationofactionofTresibaismorethan24hrsandlastsupto42hours.
YoucaninjectTresibasubcutaneouslyoncedailyatanytimeofday.

44. 6.PremixedInsulin
Premixedinsulinisacombinationoftwodifferenttypesofinsulin.Itisafixed
compositionofrapidorshort-actingandintermediate-orlong-actinginsulin.
Intermediate-actinginsuliniscommonlyusedwithultra-shortandshort-acting
insulintopreparepremixedinsulin.
Thisisacombinationofbolusandbasalinsulinanalogue.
Premixedinsulinformulationsareselectedaccordingtopatientcharacteristicsand
basedonglycemicpatternstomanagediabetesmellitus.
Thesepremixedinsulininjectionscanbeinjectedonce,twiceorthriceasper
patientrequirement.
Premixedinsulinisavailableindifferentcombinations–
Combinationofintermediateandultra-short-actinginsulin
Despiteusingintermediateinsulin,theyhaveaquickeronsetofaction.So,you
needtoinjecttheseinjectionsbefore1515-minutemeal.
Theexamplesare–
●HumalogMix25(InsulinLispro25%+InsulinLisproProtamine75%)
●HumalogMix50(InsulinLispro50%+InsulinLisproProtamine50%)
●NovoMix30(30%insulinaspartand70%insulinaspartprotamine)

47. Combinationofintermediateandshort-actinginsulin

48. Youcanseethisbiphasichumaninsulinin–
●Wosulin(30%solubleinsulinand70%isophaneinsulin)
●HumanMixtard70/30(70%InsulinIsophane/NPH70%+30%Human
Insulin/SolubleInsulin)
Here,soluble/NPHinsulinisshort-acting,andIsophaneisintermediate.
Itwouldbebesttotakethisinjection30minutesbeforethemeal.
Combinationofultra-shortandultra-long-actinginsulin
Ryzodecisaclassicexampleofthiscombination.Itsignificantlycontrolsboth
fastingandpost-prandialbloodsugarlevels.
Ryzodeccontains70%insulindegludecand30%insulinaspart.
Here,Insulindegludecisultra-long-actinginsulin.WhileInsulinaspartisan
ultra-short-actinginsulin.
Itisgivenonceadayimmediatelybeforeameal.
Whatistheroleofliraglutideandexenatideindiabetes
mellitus?
Liraglutideandexenatideareincretins-baseddrugs.Theyarealsoknownasnewer
antidiabeticdrugs.Theywereintroducedin2005.

49. Theseincretin-baseddrugsarealsothelaststepmedicationoptiontocontrolhigh
bloodsugarlevels.
Although,themechanismofincretin-baseddrugsseemstobeDPP-4inhibitors.
Buttherearesomedifferencesinmechanism.DPP-4inhibitorsareincretin
enhancers.TheyindirectlyreleaseincretinsbyinhibitingtheDPP-4enzymeand
lettingtheincretingotothepancreas.
Onthecontrary,liraglutideandexenatidearesyntheticincretinssuchasGLP-1
(Glucagon-likepeptide-1).ThesedrugsarealsocalledGLP-1agonists.
TheseGLP-1agonistdrugsdirectlyreleaseinsulintopancreaticbetacells.
GLP-1agonistdrugsareavailableinthemarketininjectionforminbrandsof
●Liruglutide–VictozaandSaxendainjection
●Exenatide–Byettainjection
Itcanbeusedincombinationwithoraltripletherapy.
●Metformin+Sulfonylurea+GLP-1agonist
●Metformin+SGLT2inhibitors+GLP1agonist
●Sulfonylurea+SGLT2inhibitors+GLP1agonist
●SGLT2inhibitors+GLP1agonist
DPP4inhibitorsandGLP1agonistcombinationsarenotrecommendedinT2DM
duetoasimilarmechanism.

50. Whatisthepharmacologicalmanagementofdiabetes
mellitus?
Thereisaproperwayorrulestomanageanydisease.Thistreatmentplaniscalled
algorithm.
Here,wewillknowthealgorithmformanagingT1DMandT2DM.
Ifyouhavenewlydetecteddiabetes,thenthetreatmentplanshouldbestartedin
thefollowingways–
ManagementofT1DM(Type1DiabetesMellitus)
IfapatienthasT1DM,therewouldbefewoptions.Itshouldbestartedwithdiet
control,exerciseandInsulininjections.
ManagementofT2DM(Type2DiabetesMellitus)
IfyouhaveT2DMandyourbloodsugarlevelisnotcontrolledbydiet
modificationandexercise.
STEP1–Mono-therapy
Theprimarygoalofmono-therapyistoHbA1c<7.5%.
Metforminisaninitialtherapy(orFirst-linedrug)fortreatingT2DM.Youshould
beon–
Dietcontrol+exercise+Metformintablet
IfMetforminiscontraindicatedorintolerant.Inthatcase,thefollowingdrugs
shouldbeadded–
●Sulphonylureas

51. ●OrDPP4inhibitors“gliptins,”e.g.Sitagliptin,linagliptin,etc.
●OrSGLT2inhibitors“gliflozins,”e.g.dapagliflozin,empagliflozinand
canagliflozin
●OrPioglitazone
STEP2–Dualtherapy
YourdoctormaystartdualtherapyifHbA1C>7.5%.
Fornon-obesepatient
●Metformin+Sulfonylurea,or
●Sulfonylurea+Pioglitazone(Ifmetforminiscontraindicatedorintolerant)
Forobesepatient
●Metformin+DPP4inhibitorsorSGLT2inhibitorsorPioglitazone
IfMetforminiscontraindicatedorintolerant.Inthatcase,thefollowingdrugs
shouldbeadded–
●Sulfonylurea+DDP4inhibitors
●OrSulfonylurea+Pioglitazone
●OrDPP4inhibitors+Pioglitazone
●OrSGLT2inhibitors+Sulphonylureas

52. STEP3–TripleTherapy
YoumayrequiretripletherapyifHbA1C>9%.Itcanbestartedincombination
withmetforminandotherantidiabeticdrugs–
●Metformin+Sulfonylurea+SGLT2inhibitors
●Or,Metformin+Sulfonylurea+DPP4inhibitors
●Or,Metformin+Sulfonylurea+Pioglitazone
●Or,Metformin+Pioglitazone+SGLT2inhibitors
IfmetforminisintolerantorContraindicated,thenthepatientwillrequire
injectabletherapy(Step4)
STEP4–Injectablewithcombinations
Therearethreeoptionsincombination;itcanbestartedasperyourneedandbased
onglycemicpattern–
Option1–OralTripletherapywithGLP1
●Metformin+Sulfonylurea+GLP-1
●Metformin+SGLT2inhibitors+GLP1
●Sulfonylurea+SGLT2inhibitors+GLP1
●SGLT2inhibitors+GLP1

53. Note–DonotuseDPP4andGLP1incombination.
Option2–OralTripleTherapywithInsulin
●Metformin+Sulfonylurea+Insulin
●Metformin+SGLT2inhibitors+Insulin
●Metformin+DPP4inhibitors+Insulin
●Sulfonylurea+DPP4inhibitors+Insulin
●Sulfonylurea+SGLT2inhibitors+Insulin
●SGLT2i+DPP4inhibitors+Insulin
●SGLT2i+Insulin
Option3–GLP1andInsulin
Conclusion
Lifedoesnotendwithdiabetes;itcanbemanagedbylifestylemodification.
Thebestwaytomanagediabetesistoeducatethepatient.Patientsshouldbeaware
oftheirdietandexercise.Theyshouldknowwhatantidiabeticmedicineshave
beenprescribed.
Therearepropersteps(oralgorithms)ofantidiabeticmedicinestomanagediabetes
mellitus.

54. Agooddoctoralwaysfollowsthealgorithmforthetreatmentofdiabetesmellitus.
Thisposthasdiscussedtheantidiabeticdrugclassification,mechanism,uses,
dosage,andsideeffects.
Theseantidiabeticmedicinesplayasignificantroleincontrollingyourbloodsugar
level.
Ifyoufoundthispostinformative,pleaseshareitonsocialmedia.
References–
1.D.Tripathi,Essentialsofmedicalpharmacology,7thEdition.Jaypee
BrothersMedicalPublishers(P)Ltd;2013.Chapter–19,Insulin,oral
hypoglycemicagentsandglucagon,Page–258.
2.Diabeteseducationonline,universityofCalifornia.https://dtc.ucsf.edu/
3.Electronicmedicinescompendium(EMC)
https://www.medicines.org.uk/emc
4.Nationalclinicalguidelinesformanagementofdiabetesmellitus,2010,first
edition.
5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995498/
6.https://www.medicines.org.uk/emc/product/594/smpc

55. 7.https://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/me
dications-and-therapies/type-2-non-insulin-therapies/insulin-sensitizers/
8.https://pubmed.ncbi.nlm.nih.gov/11921433/
FAQ
Q1.Whatisthefirstdrugofchoicefordiabetes?
Metforministhefirstdrugofchoicefortype2diabetesmellitus(T2DM).This
medicineshouldbestartedinitiallyinnewlydetecteddiabetespatients.
Q2.Whichantidiabeticdrugclassleadtoglycosuria?
TheSGLT2inhibitors(dapagliflozin,empagliflozinandcanagliflozin)havea
uniquemechanismtoexcreteglucosefromurine.Duetothis,youmayhavea
glycosuriaeffect.
Q3.Whatisthenewdrugfordiabetes?
GLPagonists(Liraglutideandexenatide),DPP4inhibitors(gliptins),andSGLT2
inhibitors(Gliflozins)areconsiderednewerdrugsfordiabetesmellitus.Still,the
FDAapprovedBaxagliflozin(SGLT2inhibitors)onJan23,2023.
Q4.Isrepaglinidesafeforkidneys?
Yes.Repaglinideisanabsolutelysafeandwell-tolerateddruginkidneydisease
patientswithtype2diabetesmellitus.
Q5.Islinagliptinsafeforkidneys?

56. Linagliptinismainly(90%)excretedviafaecesbyhepatobiliaryroute.Itis
excretedinsmallquantities(1to6%)throughurine.So,Linagliptin(Trajenta)is
safeforkidneydiseasepatients.
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