nateglinide
Brand: Starlix
Prototype: repaglinide
Drug Class: meglitinide
Drug Family: antidiabetic
Subclass: amino acid-derived short-acting insulin secretagogue
Organ Systems: endocrine
Mechanism of Action
D-phenylalanine derivative that binds the SUR1 subunit of beta-cell KATP channels, triggering rapid insulin secretion. Has an even shorter duration of action than repaglinide, with action closely coupled to the postprandial glucose peak.
SUR1 subunit of KATP channels (beta cells)
Indications
- type 2 diabetes mellitus (mealtime)
Contraindications
- type 1 diabetes
- DKA
Adverse Effects
Common
- hypoglycemia
- diarrhea
- upper respiratory infections
Serious
- severe hypoglycemia (less than repaglinide)
Pharmacokinetics (ADME)
| Absorption | rapidly absorbed; peak in 1 hour |
| Distribution | 98% protein bound |
| Metabolism | hepatic via CYP2C9 (70%) and CYP3A4 (30%) to weakly active metabolites |
| Excretion | renal (83%) and fecal |
| Half-life | 1.5 hours |
| Onset | 20 minutes |
| Peak | 1 hour |
| Duration | 2–4 hours |
| Protein Binding | 98% |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP2C9 inhibitors (fluconazole) | increased nateglinide exposure | moderate |
| rifampin | CYP induction reduces nateglinide levels | moderate |
Nursing Considerations
- Administer 1–30 minutes before meals; skip dose if meal is skipped.
- Lower hypoglycemia risk than repaglinide due to shorter duration and more glucose-sensitive action.
- Less potent than repaglinide for HbA1c reduction; generally used when only modest glucose control is needed.
- Monitor renal function; renally excreted but dose adjustment not typically needed unless severe renal impairment.
Clinical Pearls
- Nateglinide's unique glucose sensitivity means its effect diminishes when blood glucose is near normal, providing a built-in protection against hypoglycemia compared to sulfonylureas.
- Among meglitinides, nateglinide has the shortest duration of action and lowest HbA1c-lowering potency, making it most suitable for isolated postprandial hyperglycemia.
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.