What is the name and mechanism of action of Repaglinide (a medication for type 2 diabetes)?

Repaglinide: Name and Mechanism of Action

Repaglinide is a meglitinide (glinide) class oral antidiabetic medication that lowers blood glucose by stimulating rapid, glucose-dependent insulin release from pancreatic beta cells through closure of ATP-dependent potassium channels. 1

Drug Classification and Chemical Structure

• Repaglinide belongs to the glinide class of insulin secretagogues, specifically classified as a carbamoylmethyl benzoic acid derivative that is chemically unrelated to sulfonylurea insulin secretagogues 1
• The molecular formula is C27H36N2O4 with a molecular weight of 452.6 1

Mechanism of Action

Repaglinide works through a highly specific cellular mechanism:

• Binds to characterizable sites on ATP-dependent potassium channels in pancreatic beta-cell membranes, causing channel closure 1
• This potassium channel blockade depolarizes the beta-cell, leading to opening of calcium channels 1
• The resulting increased calcium influx induces insulin secretion from the pancreas 1
• Insulin release is glucose-dependent and diminishes at low glucose concentrations, which provides some protection against hypoglycemia 1
• The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle, minimizing cardiac effects 1

Key Distinguishing Features from Sulfonylureas

While repaglinide stimulates insulin release like sulfonylureas, it differs in several critical ways:

• Binds to a different receptor site on the beta-cell compared to sulfonylureas 2
• Has a rapid onset and short duration of action, allowing for flexible meal-related dosing 3, 4
• Must be taken immediately before meals (typically 3 times daily) rather than once or twice daily like most sulfonylureas 5
• Demonstrates a lower risk of severe hypoglycemia compared to sulfonylureas, with approximately 60% reduction in severe hypoglycemic episodes 4

Clinical Pharmacodynamics

• Plasma insulin levels increase after meals and revert toward baseline before the next meal, mimicking physiologic insulin secretion patterns 1
• Achieves dose-proportional glucose lowering over the full dose range (0.5-4 mg per meal) 1
• Most of the fasting blood glucose-lowering effect is demonstrated within 1-2 weeks of therapy initiation 1
• In clinical trials, repaglinide reduced HbA1c by 0.5% to 1.5% 5

Excretion Profile

• Excretion occurs almost entirely by non-renal mechanisms (predominantly hepatic), making it suitable for patients with renal impairment 2
• This hepatic elimination profile distinguishes it from many sulfonylureas that require renal dose adjustment 4