THE ROLE OF ORAL HYPOGLYCEMIC AGENT IN THE MANAGEMENT OF TYPE 2 DIABETES MELLITUS

Pelatihan Penatalaksanaan Diabetes Mellitus Bagi InternisWDF Project bekerjasama dengan PB PERKENIPERKENI Cabang YogyakartaMaret 2007

CORE DEFECTS IN TYPE 2 DIABETES MELLITUS

Defect of insulin secretion

Hepatic gluconeogenesis

Glucose uptakeby peripheral tissues

HYPERGLYCEMIA

THE CHALLENCE OF TYPE 2 DIABETES MANAGEMENT

The core defect: insulin secretion and insulin resistance

Comorbid (hypertension, obesity, dyslipidemia) Data are not sufficient to support a

recommendation of one class of glucose-lowering agents, or one combination of medication with regard to effects on complications (Nathan et al., 2006)

A1C ≥7% should serve as a call to action to initiate or change therapy (Nathan et al., 2006)

ALGORUTHM FOR THE METABOLIC MANAGEMENT OF TYPE 2 DIABETES

DIAGNOSIS

LIFESTYLE INTERVENTION + METFORMIN

A1C ≥7%NO YES

ADD BASAL INSUL-Most effective

ADD SULFONYLUREA-Least expensive

ADD GLITAZONE-No hypoglycemia

A1C ≥7% A1C ≥7% A1C ≥7%NO YES NO YES NO YES

INTENSIFY INSULIN ADD GLITAZONE ADD BASAL INSULIN ADD SULFONYLUREA

A1C ≥7% A1C ≥7%NO YES NO YES

ADD BASAL OR INTENSIFY INSULIN

INTENSIVE INSULIN + METFORMIN +/- GLITAZONENathan et al. 2006; ADA, 2007

TETRATION OF METFORMIN

Begin with low-dose metformin (50 mg) taken one or twice per day with meals (breakfast and/or dinner)

After 5-7 days, if GI side effects have not occurred, advance dose to 850 or 1,000 mg before breakfast and dinner

If GI side effects appear as doses advanced, can decrease to previous lower dose and try to advance dose at a later time

The maximum effective dose is usually 850 mg twice per day, with modestly greater effectiveness with doses up to 3 g per day (Nathan et al., 2006)

SPECIAL CONSIDERATIONS

Severely uncontrolled diabetes with catabolism: FBG >250 mg/dl; random glucose levels consistently >350 mg/dl; or the presence of ketonuria; or as symptomatic diabetes with polyuria, polydipsia, and weight loss

INSULIN IS THE CHOICE

ORAL HYPOGLYCEMIC AGENTS AVAILABLE IN INDONESIAClass Generic Patent Mg/tab Daily

doseDuration

(h)

Freq. Time Metabolism

Excretion

Sulfon-ylureas

Glinide

TZD

Chlorpropamide

Glibenclamide

Glipizide

Gliclazide

Gliquidone

Glimepiride

Repaglinide

Nateglinide

Rosiglitazone

Pioglitazone

Diabenese

Daonil

Glucotrol

Diamicron

Glurenorm

Amaryl

NovoNorm

Starlix

Avandia

Actos

100, 250

2.5; 5

5; 10

80

30

1; 2; 3; 4

0.5; 1; 2

120

4

15; 30

100-500

2.5-15

2.5- 40

80-320

30-120

0.5-6

1.5-6

360

4-8

15-45

24-36

12-24

12-18

10-20

6-8

24

2-6

-

24

24

1

1-2

1-2

1-2

2-3

1

3

3

1

1

a.C

a.C

a.C

a.C

a.c

a.C

a.C

-

hepatic Renal

Renal, intestinal

Renal,intestinal

intestinal

Ren, Int.

ORAL HYPOGLYCEMIC AGENTS AVAILABLE IN INDONESIA

Class Generic Patent Mg/tab Daily dose

Duration (h)

Freq. Time Metabolism

Excretion

α-Gluco-sidase inhibitor

Biguanide

Acarbose

Metformin

Glucobay

Glucophage

50;100

500-850

100-300

250-3,000

<4

6-8

3

1-3

With meal

With or after meal

Intestinal Intestinal, renal

renal

EVIDENCE BASED MEDICINE (Montori et al., 2001)

Sulfonylureas decrease A1c by 1-2% (level 1A); weight gain 2 to 3 kg (level 1A)

Biguanides decrease A1c by 1-2% (level 1A), less weight gain, less hypoglycemia (level 1A)

α-glucosidase inhibitor decreases A1c by 0.7 to 1.8% (level 1A)

TZD as monotherapy decreases A1c by 0.9 to 1.5% (level 1A)

Meglitinide analogue decreases A1c by 1 to 2% (level 1A)

OTHER ORAL HYPOGLYCEMIC AGENTS

Insulin sensitizer: non-TZD (Glitazar, non-glitazar) Intestinal enzyme inhibitor: α-amylase inhibitor

(Tendamistase) Other specific type: DPP-IV inhibitor, amylin

analogues (pramintide) Fixed dose combination type: glucovance,

avandaryl

SITE OF ACTION

GLUCOSE INFLUX

PERIPHERALGLUCOSE UPTAKE

HEPATICGLUCOSE OUTPUT

INSULINSECRETION

HYPERGLYCEMIA

Α-glucosidaseinhibitor

Metformin

TZDMetformin

Insulinsecretagogue