Repaglinide

Brand Names: Novonorm

Drug Class: Meglitinide

Overview

Repaglinide is a meglitinide-class oral antidiabetic agent used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner, primarily reducing postprandial hyperglycemia. It should not be used in type 1 diabetes or for diabetic ketoacidosis.

Mechanism of Action

Repaglinide is a meglitinide derivative that lowers blood glucose by stimulating insulin release from pancreatic beta cells. It binds to ATP-sensitive potassium channels on beta cell membranes, leading to channel closure, membrane depolarization, calcium influx, and subsequent insulin secretion. This action is glucose-dependent, with minimal effect at low glucose concentrations.

Indications

  • Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Common Doses

  • 0.5 mg
  • 1 mg
  • 2 mg

Dosage

Typically administered 15-30 minutes before meals, 2-4 times daily depending on meal patterns. Starting dose is usually 0.5-2 mg before each meal, with maximum recommended dose of 16 mg per day. Dose should be individualized based on glycemic response and adjusted at 1-2 week intervals.

Black Box Warning

Black box warning: Concomitant use with gemfibrozil is contraindicated due to 8.1-fold increase in repaglinide exposure and severe hypoglycemia risk

Contraindications

  • Concomitant use with gemfibrozil
  • Known hypersensitivity to repaglinide or any inactive ingredients
  • Type 1 diabetes mellitus
  • Diabetic ketoacidosis

Side Effects

  • Hypoglycemia
  • Upper respiratory tract infection
  • Headache
  • Arthralgia
  • Back pain
  • Diarrhea
  • Constipation
  • Nausea
  • Weight gain

Interactions

  • Gemfibrozil: Contraindicated - 8.1-fold increase in repaglinide exposure
  • Clopidogrel: Avoid concomitant use - 3.9-5.1-fold increase in exposure
  • Cyclosporine: Limit maximum dose to 6 mg daily
  • CYP2C8 inhibitors (trimethoprim, montelukast, deferasirox): May require dose reduction
  • CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin): May require dose reduction
  • CYP inducers (rifampin, barbiturates, carbamazepine): May require dose increase
  • Other antidiabetic agents: Increased hypoglycemia risk
  • Beta-blockers, clonidine: May mask hypoglycemia symptoms

Counseling Points

  • Take 15-30 minutes before meals
  • Skip dose if meal is skipped
  • Monitor blood glucose regularly
  • Recognize symptoms of hypoglycemia (sweating, dizziness, confusion)
  • Carry glucose source for hypoglycemia treatment
  • Inform healthcare providers of all medications
  • Maintain regular meal patterns and exercise
  • Avoid alcohol which can increase hypoglycemia risk