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

Pelatihan Penatalaksanaan Diabetes Mellitus Bagi Internis WDF Project bekerjasama dengan PB PERKENI PERKENI Cabang Yogyakarta Maret 2007

CORE DEFECTS IN TYPE 2 DIABETES MELLITUS


Defect of insulin secretion

Hepatic gluconeogenesis

HYPERGLYCEMIA

Glucose uptake by peripheral tissues

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 NO A1C 7% YES

ADD BASAL INSUL -Most effective NO A1C 7% INTENSIFY INSULIN NO YES

ADD SULFONYLUREA -Least expensive NO A1C 7% YES

ADD GLITAZONE -No hypoglycemia NO A1C 7% YES

ADD GLITAZONE YES

ADD BASAL INSULIN NO A1C 7%

ADD SULFONYLUREA YES

A1C 7%

ADD BASAL OR INTENSIFY INSULIN

INTENSIVE INSULIN + METFORMIN +/- GLITAZONE


Nathan 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 INDONESIA


Class Sulfonylureas Generic
Chlorpropa mide Glibenclami de Glipizide Gliclazide Gliquidone Glimepiride

Patent
Diabenese Daonil Glucotrol Diamicron Glurenorm Amaryl NovoNorm Starlix Avandia Actos

Mg/tab
100, 250 2.5; 5 5; 10 80 30 1; 2; 3; 4 0.5; 1; 2 120 4 15; 30

Daily dose
100-500 2.5-15 2.5- 40 80-320 30-120 0.5-6 1.5-6 360 4-8 15-45

Duration (h)
24-36 12-24 12-18 10-20 6-8 24 2-6 24 24 1

Freq.

Time
a.C a.C a.C a.C a.c a.C a.C

Metaboli sm
hepatic

Excretio n
Renal

1-2 1-2 1-2 2-3 1 3 3 1 1

Renal, intestinal

Glinide

Repaglinide Nateglinide Rosiglitazon e Pioglitazone

Renal,intes tinal intestinal

TZD

Ren, Int.

ORAL HYPOGLYCEMIC AGENTS AVAILABLE IN INDONESIA


Class -Glucosidase inhibitor Biguanid e Generic Acarbos e Metformi n Patent Glucoba y Glucoph age Mg/tab 50;100 Daily dose 100-300 Duration (h) <4 3 Freq. Time With meal With or after meal Metaboli sm Intestinal Excretio n Intestinal , renal renal

500-850

2503,000

6-8

1-3

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) -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: -amylase inhibitor (Tendamistase) Other specific type: DPP-IV inhibitor, amylin analogues (pramintide) Fixed dose combination type: glucovance, avandaryl

SITE OF ACTION
GLUCOSE INFLUX -glucosidase inhibitor

Insulin secretagogue

HEPATIC GLUCOSE OUTPUT

HYPERGLYCEMIA

INSULIN SECRETION

Metformin TZD Metformin

PERIPHERAL GLUCOSE UPTAKE

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