Oral Medications for Diabetes Mellitus

Alpha-Glucosidase Inhibitors

Examples and Usual Adult Dose

Acarbose (Precose) 25-100 mg tid before meals

Miglitol (Glyset) 25-100 mg tid before meals

Mechanism of Action

These drugs are reversible inhibitors of intestinal alphaglucosidase enzymes, which result in delayed breakdown of ingested carbohydrates, and which delay glucose absorption. They reduce postprandial hyperglycemia.

Adverse Effects and Clinical Notes

Adverse effects include flatulence, bloating, and other gastrointestinal (GI) complaints. Alpha-glucosidase inhibitors should be titrated gradually to limit GI intolerance. These drugs will decrease postprandial hyperglycemia and rarely produce symptomatic hypoglycemia. They should not be used in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or chronic intestinal disease associated with disorders of digestion or absorption.

First-Generation Sulfonylureas

Examples and Usual Adult Dose

Tolbutamide (Orinase) 1000-2000 mg/day

Acetohexamide (Dymelor) 250-1000 mg/day

Chlorpropamide (Diabenese) 100-250 mg/day

Tolazamide (Tolinase) 100-250 mg/day

Second-Generation Sulfonylureas

Examples and Usual Adult Dose

Glimepiride (Amaryl) 1-8 mg/day

Glyburide (DiaBeta, Micronase) 2.5-20 mg/day

Glipizide (Glucotrol) 5-40 mg/day

Micronized glyburide (Glynase) 1.5-12 mg/day

Mechanism of Action

These drugs increase pancreatic insulin secretion, in part by inactivating potassium (K+) channels on beta cells. Sulfonylurea use may result in a gradual but limited increase in endogenous insulin receptor sensitivity.

Adverse Effects and Clinical Notes

Hypoglycemia, weight gain, allergic reactions, pruritus, rash, hepatotoxicity, and photosensitivity are possible. Side effects of chlorpropamide include syndrome of inappropriate antidiuretic hormone and alcohol intolerance (it produces a disulfiram-like reaction).

Biguanides

Example and Usual Adult Dose

Metformin (Glucophage) 500-2250 mg/day

Mechanism of Action

Metformin increases hepatic and peripheral sensitivity to insulin. It also may inhibit gluconeogenesis, stimulate glucose uptake by skeletal muscle, and increase insulin receptor binding.

Adverse Effects and Clinical Notes

Metformin may cause nausea, diarrhea, flatulence, or lactic acidosis (rare). This drug should not be used in patients with significant renal impairment. It should be avoided in patients with alcohol abuse, severe hepatic impairment, and severe congestive heart failure.

Thiazolidinediones

Examples and Usual Adult Dose

Rosiglitazone (Avandia) 4-8 mg/day

Pioglitazone (Actos) 15-45 mg/day

Mechanism of Action

These drugs increase sensitization of target tissues to insulin by binding to the intracellular peroxisome proliferator- activated receptor-gamma (PPARgamma) in tissues. This results in increased expression of the glucose transporter-4 receptor, thus increasing tissue insulin sensitivity. Predominant effects are seen in the liver and skeletal muscle. In the liver, glucose uptake increases and insulin levels are decreased. Glucose uptake into muscles also is increased.

Adverse Effects and Clinical Notes

Adverse effects may include weight gain, fluid retention, and hepatic injury (rare). These drugs should be avoided in patients with Class III or IV heart failure. They typically do not cause symptomatic hypoglycemia and do not increase insulin release. They are sometimes referred to as ?glitazones? or ?PPAR-gamma agonists.? Pioglitazone tends to decrease triglycerides and to increase high-density lipoprotein (HDL) cholesterol, whereas rosiglitazone may increase total cholesterol, low-density lipoprotein, and HDL.

Insulin Secretagogues

Examples and Usual Adult Dose

Repaglinide (Prandin) 0.5-4 mg tid with meals (up to 16 mg/day)

Natagrelide (Starlix) 60-120 mg tid with meals (up to 360 mg/day)

Mechanism of Action

Similar to sulfonylureas, these drugs block the adenosine triphosphate?sensitive K+ channel on beta cells, thus increasing insulin secretion. The clinical activity of insulin secretagogues is glucose-dependent, however, unlike that of sulfonylureas.

Adverse Effects and Clinical Notes

Hypoglycemia is a possible side effect. These drugs should be given with meals. A dose should be omitted if a meal is skipped or added if a meal is added.

Combination Therapies

Avandamet 1/500 - Rosiglitazone 1 mg and metformin 500 mg

Avandamet 2/500 - Rosiglitazone 2 mg and metformin 500 mg

Avandamet 4/500 - Rosiglitazone 4 mg and metformin 500 mg

Glucovance 1.25/250 - Glyburide 1.25 mg and metformin 250 mg

Glucovance 2.5/500 - Glyburide 2.5 mg and metformin 500 mg

Glucovance 5/500 - Glyburide 5 mg and metformin 500 mg

Metaglip 2.5/250 - Glipizide 2.5 mg and metformin 250 mg

Metaglip 2.5/500 - Glipizide 2.5 mg and metformin 500 mg

Metaglip 5/500 - Glipizide 5 mg and metformin 500 mg

For a list of suggested reading, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dryan@mwc.com.