Typical reductions in A1C values – Meglitinides
0.5 – 1.0%.
0.5 – 1.0%.
| CLINICAL PHARMACOLOGY
Mechanism of Action
Nateglinide is an amino-acid derivative that lowers blood glucose levels by stimulating insulin secretion from the pancreas. This action is dependent upon functioning beta-cells in the pancreatic islets. Nateglinide interacts with the ATP-sensitive potassium (K+ ATP) channel on pancreatic beta-cells. The subsequent depolarization of the beta cell opens the calcium channel, producing calcium influx and insulin secretion. The extent of insulin release is glucose dependent and diminishes at low glucose levels. Nateglinide is highly tissue selective with low affinity for heart and skeletal muscle
INDICATIONS AND USAGE
1) Known hypersensitivity to the drug or its inactive ingredients.
Dosing (Adults): Management of type 2 diabetes mellitus: Oral: Initial and maintenance dose: 120 mg 3 times/day, 1-30 minutes before meals; may be given alone or in combination with metformin or a thiazolidinedione; patients close to HbA1c goal may be started at 60 mg 3 times/day. Patients who are anorexic or NPO will need to have their dose held to avoid hypoglycemia.
Elderly: No changes in safety and efficacy were seen in patients 65 years; however, some elderly patients may show increased sensitivity to dosing.
Dosage adjustment in hepatic impairment: Increased serum levels seen with mild hepatic insufficiency; no dosage adjustment is needed. Has not been studied in patients with moderate to severe liver disease; use with caution.
| Mechanism of Action
Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations.
Repaglinide closes ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle.
INDICATIONS AND USAGE
1) Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
Dosing (Adults): Oral: Should be taken within 15 minutes of the meal, but time may vary from immediately preceding the meal to as long as 30 minutes before the meal
Dose adjustment: Determine dosing adjustments by blood glucose response, usually fasting blood glucose. Double the preprandial dose up to 4 mg until satisfactory blood glucose response is achieved. At least 1 week should elapse to assess response after each dose adjustment.
Dose range: 0.5-4 mg taken with meals. Repaglinide may be dosed preprandial 2, 3 or 4 times/day in response to changes in the patient’s meal pattern. Maximum recommended daily dose: 16 mg.
Patients receiving other oral hypoglycemic agents: When repaglinide is used to replace therapy with other oral hypoglycemic agents, it may be started the day after the final dose is given. Observe patients carefully for hypoglycemia because of potential overlapping of drug effects. When transferred from longer half-life sulfonylureas (eg, chlorpropamide), close monitoring may be indicated for up to >/= 1 week.
Combination therapy: If repaglinide monotherapy does not result in adequate glycemic control, metformin or a thiazolidinedione may be added. Or, if metformin or thiazolidinedione therapy does not provide adequate control, repaglinide may be added. The starting dose and dose adjustments for combination therapy are the same as repaglinide monotherapy. Carefully adjust the dose of each drug to determine the minimal dose required to achieve the desired pharmacologic effect. Failure to do so could result in an increase in the incidence of hypoglycemic episodes. Use appropriate monitoring of FPG and Hb A1c measurements to ensure that the patient is not subjected to excessive drug exposure or increased probability of secondary drug failure. If glucose is not achieved after a suitable trial of combination therapy, consider discontinuing these drugs and using insulin.
Dosing adjustment in renal impairment:
| Meglitinides lower blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations. Meglitinides interact with the ATP-sensitive potassium (K+ ATP) channel on pancreatic beta-cells. The subsequent depolarization of the beta cell opens the calcium channel, producing calcium influx and insulin secretion.
They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped. Adverse reactions include weight gain and hypoglycemia.
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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