Meglitinides

Meglitinides are a class of oral antidiabetic drugs used in the management of type 2 diabetes mellitus. They function as insulin secretagogues, stimulating pancreatic beta cells to release insulin by binding to the SUR1 subunit of ATP‑sensitive potassium channels on the beta‑cell membrane. Inhibition of these channels leads to cell depolarization and calcium‑mediated insulin release. The agents are short‑acting and are taken just before meals, so their insulinotropic effect largely follows meal intake and helps control postprandial glucose elevations.

The two main members are repaglinide and nateglinide. They have rapid onset (typically within 15–60 minutes) and a short duration of action, usually a few hours. Patients take a dose before each meal; if a meal is skipped, the corresponding dose is skipped as well. They are metabolized mainly in the liver via cytochrome P450 enzymes and are excreted in the bile; dosing may need adjustment in hepatic impairment.

Clinical use: meglitinides are used as second‑line therapy for type 2 diabetes when metformin alone is insufficient or in patients who prefer shorter‑acting secretagogues or have irregular meal patterns. They can be combined with metformin or other agents, but are not typically used in type 1 diabetes or diabetic ketoacidosis. Caution is needed in patients with hepatic disease, elderly individuals, and those with a high hypoglycemia risk.

Adverse effects include hypoglycemia and weight gain. The risk of hypoglycemia can be increased if meals are skipped or if drug interactions reduce glucose intake. A notable interaction is with gemfibrozil, which substantially raises repaglinide exposure and generally requires avoidance or dose adjustment of the secretagogue.