Second Generation Sulfonylureas

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Information about Second Generation Sulfonylureas

The second generation sulfonylureas include glyburide (also known as glibenclamide), gliclazide, glipizide, and glimepiride, which are oral hypoglycemic agents that are widely used in therapy of type 2 diabetes.

Liver safety of Second Generation Sulfonylureas

These agents are known, but infrequent causes of clinically apparent liver injury.

Mechanism of action of Second Generation Sulfonylureas

The sulfonylureas are substituted arylsulfonylureas, their differences being in the types of substitutions at the two ends of the molecule. The sulfonylureas lower blood glucose through an increase in secretion of insulin from pancreatic beta cells. They may also have other extra-pancreatic hypoglycemic actions that are important during prolonged therapy. The second generation sulfonylureas have largely replaced the first generation agents in routine use, because they are more potent, can be administered in lower doses, and can be given on a once daily basis.

First line of therapy for type 2 diabetes

These agents are recommended as a first line of therapy for type 2 diabetes, but should be administered in conjunction with advice on diet and exercise. The sulfonylureas can also be used in combination with other hypoglycemic agents such as metformin, pioglitazone, alpha glucosidase inhibitors, incretin based drugs or insulin. Because of the similarity of mechanism of action, the sulfonylureas are not recommended to be used in combination with the metiglinides such as nateglinide and repaglinide.

Side effects of Second Generation Sulfonylureas

Common side effects of the second generation sulfonylureas include headache, dizziness, paresthesias, abdominal discomfort, nausea and weight gain. These agents are also associated with an “antabuse” like response to alcohol (although less likely that with first generation sulfonylureas) and patients should be advised not to drink alcoholic beverages. All sulfonylureas can cause hypoglycemia. The second generation sulfonylureas are all labelled with a special warning about increased risk for cardiovascular mortality.

Glyburide

Glyburide (glye' bure ide), which is known in other countries as glibenclamide, is available in generic forms and under the brand name of DiaBeta and Micronase in tablets of 1.25, 2.5 and 5 mg, the recommended dose initially being 1.25 to 5 mg daily, with increases based upon blood glucose and tolerance to a maximum of 20 mg daily, either in a single or divided dose. Micronized formulations are also available in tablets of 1.5, 3 and 6 mg, that may provide more sustained release. Fixed combinations of glyburide with metformin are also available in many generic forms and under the commercial name Glucovance.

Gliclazide

Gliclazide is available in generic forms and under the brand name of Diamicron and Dianorm in many countries, but not in the United States. The recommended dose initially is 40 to 80 mg twice daily, with increases weekly to achieve adequate glycemic control. The maximum dose is 320 mg daily.

Glimepiride

Glimepiride (glye mep' ir ide) is available under in several generic forms and the brand name of Amaryl in tablets of 1, 2 and 4 mg, the recommended dose initially being 1 to 2 mg once daily, with increases based upon blood glucose and tolerance to a maximum of 8 mg once daily. Fixed dose combinations of glimepiride with thiazolidinediones have also been marketed (with rosiglitazone as Avandaryl, and with pioglitazone as Duetact).

Glipizide

Glipizide (glip' i zide) is available in multiple generic forms and under the brand name of Glucotrol in tablets of 5 and 10 mg and as an extended release form (Glucotrol XL) in 2.5, 5 and 10 mg, the recommended dose initially being 5 to 10 mg daily, with increases based upon blood glucose and tolerance to a maximum of 15 mg (standard formulation) or 20 mg (extended release formulation) once daily. Higher doses should be given in divided doses daily to a daily maximum of 40 mg. Fixed combinations of glipizide with metformin are also available in both generic and brand name forms (Metaglip).

Antidiabetics

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