06 Oral Anti Diabetic Agents

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Clinical Practice Guidelines:Management of

Type 2 Diabetes Mellitus

(4thEdition 2!!"

Topic 6:

#ral $nti Diabetic $gents


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2

Patients achie%ing target &b$'c

Diabcare Asia IHM,

MOHAudit


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M#& $udit 2!!):

Medications prescribed

Medication n %

T*C only

+iguanides,ulphonylureas

$carbose

Metiglinides

Glitazones (TZD)-nsulin

)!

2./"2.)!/

2!'

''

2040/

'14

67.871.5

)1/

!1

0.6'1

IMH, MOH 2005


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4

Targets for Control

LeelsGlycaemic Control

3asting 414 01' mmol5l

6on7fasting 414 81! mmol5l

&b$'c


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)

Diabetes Education

D$T$&:

linical 'alation

'D*T$&

&ein+o,ce on t-e

ipo,tance o+ continos

edcation

&eie/ +o, Medication

'D*T$&

Docto, ,se *ssistant Medical $++ice,

ealt- 'dcation $++ice, Dietitian and ot-e,s

$34'T'To ,eass,e and alleiate anietTo nde,stand t-e disease its ana9eent

and coplicationTo p,oote copliance and sel+ca,e

'D*T$ ;L*

*ssess el+ca,e?>3GM?+oot ca,e>top so


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0

Dia9nosis o+ Tpe 2 Dia=etes*ll patients adised L@'>TAL' Modi+ication

@;G =*1cat Dia9nosis and @ollo/ p

=*1c

B6.5% $&

@;G B6 ol?L

LIFESTYLE

APPROACH*

Follow-up with HbA1c

after

3 months.

If HbA1c6.5%,continuewith ifest!le Approach.

If HbA1c

"6.5% on follow-

up, consi#er OAD

MONOTHERAPY.

=*1c

6.5 B8.0%

$&

@;G 6 B10 ol?LOAD MONOTHERAPY

$etformin

&'

A(I ) *++- Inhibitor )

(lini#es ) ) /0*s.&ptimise #ose of &A* aent

in the subse2uent 3-6

months.


after 3-6

months.

If HbA1c

6.5%, continue

therap!.

If HbA1c"6.5%, consi#erCOMBINATION OAD

THERAPY.

=*1c

C10.0% $&

@;G C1 ol?LCOMBINATION

THERAPY + BASAL /

PREMIXED INSULIN

THERAPY.

&'

INTENSIVE INSULINTHERAPY, contin!

M!t"o#$in.

=*1c

8.010.0% $&

@;G 101 ol?L

COMBINATION THERAPY***

$etformin with other &A*

aents A(I ) *++-

Inhibitor ) (lini#es ) Incretin

$imetic ) ) /0*s4 or withinsulin.

&ptimise #ose of &A* aents

in the subse2uent 3-6

months.


after 3-6

months.

If HbA1c

6.5%, continue

therap!.If HbA1c

"6.5%, consi#er

a##ition of INSULIN

THERAPY.

T,eatent *l9o,it- +o, t-e Mana9eent o+ T2DM

Footnote:

If symptomatic (weight loss, polyuria, etc) at any HbA1cand FPG level, consider insulin therapy

! "onsider metformin#AGI#other insulin sensitiser in appropriate patients!! $etformin is preferred %st line agent, and &' should preferably not be used as %stline

!!! Although oral agents can be used, initiation and intensification of insulin therapy is preferred based oneffectiveness and epense


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Proacti%e management of glycaemia:

Early combination approach

OAD + basal insulin

OAD + multiple dailyinsulin injections

Diet

OAD monotherapy

OAD combinations

OADs up-titration

Duration o diabetes

!

"

#

$HbA%c

&'(

%0


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#ral $gent Monotherapy:

>ecommendations

'1 -f glycaemic targets are not achie%ed (&b$'cB01)9.3PG B0 mmol5*


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"

Combination #ral $gents:

>ecommendations

'1 6e


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'!

Combination #ral $gents F

-nsulin: >ecommendations'1 6e


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''

#ral $nti7Diabetic (#$D $gents

There are currently fi%e classes of #$Dagents:

'1 $lpha7glucosidase inhibitor ($G-s

21 +iguanides

1 Dipeptidyl peptidase74 (DPP74 -nhibitors

41 -nsulin ,ecretagogues ,ulphonylureas

6on7,s or Meglitinides

)1 Thia@olidinediones (TDs


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'2

$lpha7glucosidase inhibitor ($G-s

$G-s e1g1 acarbose. act at the gut epithelium. toreduce the rate of digestion of polysaccharides inthe pro;imal small intestine by inhibiting 7glucosidase en@ymes1 They should be ta=en


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$lpha7glucosidase inhibitor ($G-s(cont1

-f hypoglycaemia occurs


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'4

+iguanides (Metformin

Metformin does not stimulate insulin secretion. andlo


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Generally


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@o,lation Mini Dose Mai Dose

Metformin)!! mg tablet

-nitial dose )!! mg #Dsual dose )!! mg TD,

Ma;imum dose'.!!! mg +D

Metformin >etard8)! mg tablet

-nitial dose 8)! mg #Dsual dose 8)! mg +D

Ma;imum dose'./!! mg #M 58)! mg #6

Metformine;tended release)!! mg tablet

-nitial dose )!! mg #D Ma;imum dose2.!!! mg #D

Glibenclamideand metforminfi;ed dosecombination

-nitial dose one '12)mg 52)!mg tablet #D or +D

Ma;imum dose t


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'/

-ncretins

The incretin effect is mar=edly decreased in T2DM.resulting in delayed and reduced insulin release as


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'8

DPP74 -nhibitor (,itagliptin

-t lo


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'"

DPP74 -nhibitor (,itagliptin (cont1

@o,lation Mini dose Mai dose

,itagliptin'!! 5 )! 5 2) mg tablet

'!! mg #D '!! mg #D

,itagliptin and metformin fi;eddose combination)! mg 5 )!! mg tablet)! mg 5 8)! mg tablet)! mg 5 '.!!! mg tablet

)! mg 5 )!! mg+D )! mg 5 '.!!!mg +D


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2!

-nsulin ,ecretagogues (,s

,s lo


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2'

-nsulin ,ecretagogues (,s (cont1

,s should be ta=en ! minutes before meals.e;cept Glimepiride and Glicla@ide M>


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22

-nsulin ,ecretagogues (,s (cont1

@o,lation Mini dose Mai dose

Glibenclamide) mg tablet

21) mg #M '! mg +D

Glicla@ide 8! mg tabletGlicla@ide M> ! mg tablet

4! mg #M! mg #M

'0! mg +D'2! mg #M

Glipi@ide) mg tablet

21) mg #M '! mg +D

Glimepiride2 mg 5 mg tablet

' mg #M 0 mg #M


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2

-nsulin ,ecretagogues

6on7,s or Meglitinides

These are short acting insulin secretagogues


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-nsulin ,ecretagogues

6on7,s or Meglitinides (cont1

-t is associated


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2)

Thia@olidinediones (TDs

TDs are pero;isome proliferator7acti%ated receptor7gamma (PP$>7N agonists and act primarily byincreasing insulin sensiti%ity of muscle. adipose tissueand li%er to endogenous and e;ogenous insulin (insulin

sensitisers Ohen used as monotherapy. TDs ha%e demonstrated a

!1)7'149 decrease in &b$'c

-mpro%ement in glycaemic control may only be seenafter si;


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Thia@olidinediones (TDs (cont1

>ecent long term studies ha%e found that both TDsha%e been associated


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G*P7' $nalogue (E;enatide

-t is gi%en parenterally. Iust before brea=fast and

dinner

-t reduces &b$'cby !1)7'1!9. sustained efficacy

o%er 2 years -t can be added to metformin and5or , if

glycaemic targets are not achie%ed

Progressi%e


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G*P7' $nalogue (E;enatide (cont1

The main ad%erse effects are gastrointestinalsymptom. notably nausea this can beminimised by starting at a lo< dose


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2"

Proacti%e management of glycaemia: early

combination approach

OAD + basal insulin

OAD + multiple dailyinsulin injections

Diet

OAD monotherapy

OAD combinations

OADs up-titration

Duration o diabetes

!

"

#

$HbA%c&

'(

%0


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!

General Guidelines for se of #$D

$gents -n elderly non7obese patients. short acting insulin

secretagogues can be started. but long acting ,s are to bea%oided1 >enal function should be monitored

Compliance may be impro%ed


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Treatment strategy

Choice of monotherapy durability of drug. fit thephenotype

More aggressi%e strategy combination therapy for

those ational use of drugs


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,ummary

Current glycaemic management of diabetes isinadeHuate Too fe< patients are achie%ing targets for &b$'c

6e< approaches are needed to impro%e outcomes

6eed to inter%ene early F more aggressi%ely1 Treat to goal. treat to phenotype. indi%idualised1

Early combination therapy but =eep regimens simple 1Early insulin initiation start simply


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Thank you

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06 Oral Anti Diabetic Agents