repaglinide
Brand: Prandin
Prototype Drug
Drug Class: meglitinide
Drug Family: antidiabetic
Subclass: short-acting insulin secretagogue
Organ Systems: endocrine
Mechanism of Action
Binds to a distinct site on the SUR1 subunit of ATP-sensitive potassium channels in beta cells, causing rapid channel closure, depolarization, and insulin secretion. Has a very short duration compared to sulfonylureas, making it suitable for mealtime-only glucose control.
SUR1 subunit of KATP channels (pancreatic beta cells)
Indications
- type 2 diabetes mellitus (mealtime insulin secretagogue)
Contraindications
- type 1 diabetes
- DKA
- concurrent gemfibrozil use (major interaction)
Adverse Effects
Common
- hypoglycemia (meal-related)
- weight gain
- headache
- back pain
Serious
- severe hypoglycemia (if meal is skipped)
- hepatotoxicity (rare)
Pharmacokinetics (ADME)
| Absorption | rapidly absorbed; peak within 1 hour; take 0–30 min before meals |
| Distribution | 98% protein bound |
| Metabolism | hepatic via CYP3A4 and CYP2C8 |
| Excretion | fecal (90%) via bile; minimal renal |
| Half-life | 1 hour |
| Onset | 30 minutes |
| Peak | 1 hour |
| Duration | 3–4 hours |
| Protein Binding | 98% |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| gemfibrozil | CYP2C8 and OATP1B1 inhibition dramatically increases repaglinide levels (8-fold); contraindicated | contraindicated |
| clarithromycin | CYP3A4 inhibition increases repaglinide levels | major |
Nursing Considerations
- Take 0–30 minutes before each meal; if a meal is skipped, skip the dose to prevent hypoglycemia.
- The gemfibrozil interaction is contraindicated and clinically critical — always check for this combination.
- Monitor liver function; avoid in significant hepatic impairment (primary route of elimination).
- Flexible dosing (2–4 times daily based on meal schedule) can accommodate irregular eating patterns better than fixed-dose sulfonylureas.
Clinical Pearls
- Meglitinides are taken with each meal, offering flexible dosing for patients with irregular eating schedules; if a meal is skipped, the dose must be skipped to avoid hypoglycemia.
- The gemfibrozil-repaglinide interaction is a landmark CYP2C8/OATP interaction used frequently in pharmacology education — coadministration is absolutely contraindicated.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.