MediNews

Drug class	Mechanism of action	Dosage	Decrease in hemoglobin A1c concentration*	Side effects	Contraindications
a-Glucosidase inhibitor (acarbose)	Delays intestinal carbohydrate absorption	25 mg once daily, titrated to 100 mg 3 times daily	0.5% - 1.0%	Gastrointestinal	Irritable bowel syndrome, severe kidney of liver dysfunction
Biguanide (metformin)	Increases liver and muscle insulin sensitivity; decreases hepatic glucose production	500 mg once daily, titrated to 1000 mg twice daily	1.0% - 1.5%	Gastrointestinal, lactic acidosis (rare)	Moderate to severe liver or cardiac dysfunction, mild renal dysfunction
Insulin secretagogue Sulfonylureas gliclazide,glimepiride, glyburide)	Increases insulin secretion	Gliclazide 40-160 mg twice daily, 30-120 mg once daily (MR form) Glimepiride:1-8 mg once daily, Glyburide: <_ 5 mg once daily,titrated to > 5 mg twice daily	1.0% - 1.5%	Hypoglycemia, weight gain	Moderate to severe liver dysfunction; adjust dose in the presence of severe kidney dysfunction. Avoid use of glyburide in elderly patients or patients with kidney dysfunction
Non-sulfonylureas repaglinide,nateglinide)	Acute increase of insulin secretion	Repagliinide: 0.5 - 4 mg 3 times daily Nateglinide: 60 - 120 mg 3 times daily	Repaglinide: 1.0 % - 1.5% Nateglinide: 0.5% - 1.0%	Hypoglycemia, weight gain	Severe liver of kidney dysfunction; avoid concomitant use of repaglinide with gemfibrozil
Insulin sensitizer or thiazolidinediones rosiglitazone, pioglitazone)	Increase adipose and muscle insulin sensitivity	Rosiglitazone:2-8 mg once daily Pioglitazone:15-45 mg once daily	1.0% - 1.5%	Weight gain, edema, anemia, pulmonary edema, CHF	Severe liver dysfunction, NYHA class II-IV CHF
Intestinal lipase inhibitor ¦ (orlistat))	Decreases intestinal fat absorption weight loss)	120 mg 3 times daily	0.3% - 0.9%	Gastrointestinal, reduced absorption of fat-soluble vitamins	Malabsorption syndrome, cholestasis
Note: MR = modified release, CHF = congestive heart failure, NYHA = New York Heart Association. * Indicated average decreases in hemoglobin A1c concentrations after 3-6 months of monotherapy.s Preferred primary agent for overweight patients. ¤ Use with caution or avoid in the presence of any elevation in serum creatinine levels. f 6-12 weeks are required to achieve the full glucose-lowering effect. ¦ Suitable for obese patients only
Table 6 : Orally administered antihyperglycemic agents (OHAs) for the treatment of Diabetes

Biguanides

Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Metformin has become the most commonly used agent for type 2 Diabetes patient.
● Metformin ● Phenformin

Thiazolidinediones

Thiazolidinediones, also known as Glitazones bind to Peroxisome Proliferator Activated Receptor g (PPARg), a type of nuclear regulatory protein involved in transcription ofnumerous genes regulating glucose and fat metabolism. They act as Insulin sensitizers without increasing insulin secretion.

● Rosiglitazone ● Pioglitazone ● Troglitazone

Alpha glucosidase inhibitors
Alpha glucosidase inhibitors are Diabetes pills but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity. These agents can be helpful in combination with other agents in type 2 Diabetes.
● Miglitol ● Acarbose

Combined oral drug treatment
The followings are the recommended combination oral therapy for Diabetes patients :
● Older sulphonylureas plus metformin
● Newer sulphonylureas plus metformin
● Meglitinide (nateglinide, repaglinide) plus metformin
● Older sulphonylureas plus metformin
● Newer sulphonylureas plus metformin
● Meglitinide plus metformin