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INSULIN SECRETAGOGUE: MEGLITINIDE
Repaglinide is the first member of the meglitinide group ofinsulin secretagogues (Table 41–7). These drugs modulate beta-cell insulin release by regulating potassium efflux through the potassium channels previously discussed. There is overlap with the sulfonylureas in their molecular sites of action because the megli-tinides have two binding sites in common with the sulfonylureas and one unique binding site.
Repaglinide has a very fast onset of action, with a peak concen-tration and peak effect within approximately 1 hour after inges-tion, but the duration of action is 4–7 hours. It is hepatically cleared by CYP3A4 with a plasma half-life of 1 hour. Because of its rapid onset, repaglinide is indicated for use in controlling post-prandial glucose excursions. The drug should be taken just before each meal in doses of 0.25–4 mg (maximum 16 mg/d); hypogly-cemia is a risk if the meal is delayed or skipped or contains inadequate carbohydrate. This drug should be used cautiously in individuals with renal and hepatic impairment. Repaglinide is approved as monotherapy or in combination with biguanides.There is no sulfur in its structure, so repaglinide may be used in type 2 diabetics with sulfur or sulfonylurea allergy.
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