INTERVENTION IN T2DM

KLINIK DIABETES TERPADU RS ISLAM KLATEN

Principals Intervention in T2DM

Education Medical nutrition therapy Physical activity Pharmacologic intervention

Hyperglycemia in T2DM
Defect of insulin secretion

Hepatic glucose production

HYPERGLYCEMIA

Carbohydrate absorption

Glucose uptake by muscle & adipose tissue

Intervention
Defect of insulin secretion
Insulin Insulin secretagogue Carbohydrate absorption

Insulin Metformin Hepatic glucose production

HYPERGLYCEMIA

Thiazolidinedione Metformin Insulin

Alpha-glucosidase inhibitor
Glucose uptake by muscle and adipose tissue

Insulin Secretagogue

Sulfonylureas: Use as adjunct to diet and exercise. Stimulate insulin secretion by blocking K+ channel of the beta cell. Potential adverse effect: hypoglycemia, hypersensitivity, weight gain. EBM: decrease A1c by 1 to 2% (level 1A), cause weight gain of a proximately 2 to 3 kg (level 1A), major hypoglycemia 1 to 2% of patients receiving sulfonylureas.

Insulin Secretagogue

Meglitinde analogues (repaglinide, nateglinide): stimulate release of insulin in response to a glucose load (meal). One meal one dose, fast on fast off. Contraindications: diabetic ketoacidosis, T1DM, hypersensitivity. Adverse effects: hypoglycemia, hypersensitivity, weight gain. EBM: decrease A1c by 1 to 2% (level 1A), not significantly different from that seen with sulfonylureas (level 1A), hypoglycemia is similar with sulfonylueas (level 1A).

Biguanid

Metformin: has insulin sensitizing properties. Decreases hepatic glucose production by improving insulin action at the liver. Contraindications: prone to metabolic acidosistates or hypoxic states Adverse effect: lactic acidosis, anorexia, nausea, diarrhea EBM: it is associated with a 1 to 2% decrease in A1c (level 1A), similar to that of sulfonylureas (level 1A)

Alpha-Glucosidase Inhibitor

Acarbose (Glucobay): inhibiting -glucosidase enzymes there by slowing digestion of ingested carbohydrates, delaying glucose absorption. Contraindications: major gastrointestinal disorders. Adverse effects: flatulence, abdominal bloating. EBM: decreases A1c by 0.7 to 1.8% (level 1A)

Thiazolinediones (insulin sensitizer)

Pioglitazone, Rosiglitazone: It enhances tissue sensitivity to insulin in muscle through activation of intracellular receptors. Contraindications: hypersensitivity, active liver disease, congestive heart failure. Adverse effects: weight gain, idiosyncratic hepatocellular injury or necrosis. EBM: reduce A1c by 0.9 to 1.5% (level 1A)

Oral Hypoglycemic Agents

Class Sulfonylureas Chlorpropamide Tolbutamide Trade names (mg) Diabenese 100 & 200 Rastinon 500 Renabetik 2.5-5 Glucotrol XL 5-10 Diamicron Glucodex 80 Glurenorm 30 Daily dose (mg) 100-500 500-2000 Initial dose (mg) 50 Duration of action (h) 24-36 6-12 1 2-3 Freq.

Glibenclamide
Glipizide Glicazide Gliquidone

2.5-20
5-20 80-240 30-120

2.5
5 40 15

12-24
10-16 10-20 10-20

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

Oral Hypoglycemic Agents

Class Sulfonylureas Glimepiride Repaglinide Nateglinide Biguanide Metformin Trade Daily dose names (mg) (mg) Amaryl 1-4 Novonorm 0.5-16 Starlix 360 Diabex, 250-3000 250 glumin, glucophage Glucobay 75-300 50 50-100 10-20 Initial dose (mg) Duration of action (h) Freq.

1 2-4 2-4 1-3

Acarbose TZD Pioglitazone Rosiglitazone

Actos
Avandia

15-45 2-8

1 1 or 2

Insulin
Type Short acting: Regular insulin Actrapid Humulin R Intermediate: Insulatard Humulin N Long acting: Lantus Mixed: mixtard, humulin 30/70 Rapid acting: lispro, aspart, gluilysine Initiation (h) 0.5-1 2-4 Peak (h) Duration (h) 5-8

1-2

4-12

8-24

2 0.5-1 <30 minute

6-20 2-4 & 6-12 1

18-36 8-24 3-4