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For nearly 50 years, sulfonylureas, derived from sulfonic acid and urea, have had a central role in oral hypoglycemic therapy of T2DM. Sulfonylureas increase endogenous insulin secretion and can only be used in individuals that have retained significant b-cell function. The combination of efficacy, low incidence of adverse events, and low cost has contributed to their success and continued use. Sulfonylureas are generally safe and are relatively inexpensive. Hypoglycemia is the most common adverse event that is encountered with their use. First-generation

Table 6 Summary of oral antidiabetic therapies

Diet and exercise

Sulfonylureas and glitinides Metformin a-Glucosidase Inhibitors


Table 6 Summary of oral antidiabetic therapies

Primary mechanism

Typical improvement in HbA1C Typical improvement in FPG

k Insulin resistance 0.5-2.0%

t Insulin secretion

1.0-2.0% 60-75 mgdL "1 3.3-4.2 mmol L "1

k Hepatic glucose output

1.0-2.0% 50-70 mgdL "1 2.8-3.9 mmol L "1

k GI absorption of carbohydrates 0.5-1.0% 25-30 mgdL "1 1.9-2.2 mmol L "1

t Insulin sensitivity

0.5-1.0% 60-80 mgdL "1 3.3-4.3 mmol L "1

Recommended starting dose

Caloric restriction to reduce weight by 1-2 kg month _ 1

Glyburide 1.25 mg day _ 1 Glipizide 2.5 mg day _ 1 Glimepiride 1mgday _ 1 Nateglinide 60 mg before meals Repaglinide 0.5 mg before meals

Metformin 500 mg before breakfast and dinner

Acarbose 25 mg with meals Miglitol 50 mg with meals

Rosiglitazone 4 mg day _ 1 Pioglitazone 7.5mgday_ 1

Maximal daily dose

Can use meal substitutes or add orlistat or sibutramine

Glyburide 20mgday _ 1 Glipizide 40mgday _ 1 Glimepiride 8mgday _ 1 Nateglinide 120 mg before meals Repaglinide 16mgday _ 1 (4mg before meals)

Metformin 2550 mg day _ 1 (850 mg with each meal)

Acarbose 300 mg day _ 1 (100 mg with each meal) Miglitol 300 mg day "1

Rosiglitazone 8mgday _ 1 Pioglitazone 45 mg day _ 1 (100 mg with each meal)

Effect on weight Effect on lipids

Decrease m HDL k LDL

k Triglycerides

Increase 2 HDL 2 LDL 2 Triglycerides

Decrease t HDL k LDL

k Triglycerides

No effect 2 HDL 2 LDL 2 Triglycerides

Increase t HDL

2 or tt LDL 2 or k Triglycerides

Adverse effects Major contraindications

Injury None

Hypoglycemia Weight gain

Impaired renal function

GI symptoms Lactic acidosis

Impaired renal function Impaired hepatic function Congestive heart failure

Weight gain Flatulence GI discomfort Intestinal Disease

Weight gain Edema

Hepatotoxicity Impaired hepatic function Congestive heart failure

Agents used in combination



Metformin a-Glucosidase inhibitors



Metformin a-Glucosidase inhibitors Thiazolidinediones

Sulfonylureas Glitinides a-Glucosidase inhibitors






Metformin a-Glucosidase inhibitors Insulin

co cd sulfonylureas possess a lower binding affinity for the ATP-sensitive potassium channel and thus require higher doses to achieve efficacy. Second-generation sulfonylureas are much more potent compounds (Bl00-fold) with a rapid onset of action, shorter plasma half-lives, and longer duration of action compared with the first-generation agents57 (Table 7).

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