Meglitinides are short-acting insulin secretagogues used to control postprandial hyperglycemia.

They stimulate insulin release from pancreatic beta cells.

They have a lower risk of prolonged hypoglycemia compared to sulfonylureas.

→ Diabetes Pharmacology

Meglitinides bind to:

• Sulfonylurea receptor (SUR1)
• Component of the ATP-sensitive potassium (KATP) channel on pancreatic beta cells

Mechanism sequence:

• KATP channel closure
• Membrane depolarization
• Calcium influx
• Insulin release

Key difference from sulfonylureas:

• Very rapid onset
• Short duration of action
• Primarily affect postprandial glucose

Insulin secretion is NOT glucose-dependent, but shorter action reduces prolonged hypoglycemia risk.

• Repaglinide
• Nateglinide

• Modest HbA1c reduction
• Strong postprandial glucose lowering
• Weight gain (less than sulfonylureas)
• Lower risk of prolonged hypoglycemia

Taken before meals.

If a meal is skipped, the dose should be skipped.

• Rapid absorption
• Short half-life
• Short duration of insulin stimulation

Repaglinide is more potent than nateglinide.

Common:

• Hypoglycemia (less severe than sulfonylureas)
• Weight gain

Lower risk of prolonged hypoglycemia compared to:

• Sulfonylureas

• Type 1 Diabetes
• Use caution in hepatic impairment

Repaglinide interacts with CYP3A4 inhibitors.

Sulfonylureas:

• Longer duration
• Higher hypoglycemia risk
• Once or twice daily dosing

Meglitinides:

• Short-acting
• Meal-based dosing
• Lower prolonged hypoglycemia risk
• Target postprandial spikes

Compared to:

• Metformin → more hypoglycemia, more weight gain
• GLP-1 Receptor Agonists → less weight loss
• SGLT2 Inhibitors → no heart failure benefit

Meglitinides are useful in patients with irregular meal patterns.

• Close KATP channels like sulfonylureas
• Short-acting
• Take before meals
• Skip dose if meal skipped
• Lower prolonged hypoglycemia risk
• Target postprandial glucose

• Diabetes Pharmacology
• Sulfonylureas
• Metformin
• GLP-1 Receptor Agonists