glimepiride
Brand: Amaryl
ISMP High Alert Prototype: glipizide
Drug Class: sulfonylurea
Drug Family: antidiabetic
Subclass: third-generation sulfonylurea
Organ Systems: endocrine
Mechanism of Action
Binds SUR1 receptor to close ATP-sensitive potassium channels on pancreatic beta cells, triggering insulin secretion. Has the lowest hypoglycemia risk among second/third generation sulfonylureas due to its glucose-sensitive binding — it partially dissociates from SUR1 when glucose levels fall.
SUR1 subunit of ATP-sensitive K+ channels (pancreatic beta cells)
Indications
- type 2 diabetes mellitus (monotherapy or combination)
Contraindications
- type 1 diabetes
- DKA
- sulfonamide allergy
- severe renal or hepatic impairment
Adverse Effects
Common
- hypoglycemia (lower risk than glyburide)
- weight gain
- headache
Serious
- severe hypoglycemia (rare)
- hemolytic anemia (G6PD deficiency)
- hepatotoxicity (rare)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~100% |
| Distribution | >99% protein bound |
| Metabolism | hepatic via CYP2C9 to inactive metabolites (unlike glyburide) |
| Excretion | renal (60%) and fecal (40%) |
| Half-life | 5–9 hours |
| Onset | 1 hour |
| Peak | 2–3 hours |
| Duration | 24 hours |
| Protein Binding | >99% |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| fluconazole | CYP2C9 inhibition increases glimepiride levels | major |
| rifampin | CYP2C9 induction decreases glimepiride levels | moderate |
Nursing Considerations
- Administer with the first main meal of the day; once-daily dosing simplifies regimen.
- Preferred sulfonylurea in elderly patients over glyburide due to lower hypoglycemia risk (inactive metabolites).
- Hold dose and notify prescriber when patient is NPO; risk of hypoglycemia without caloric intake.
- Counsel patients on hypoglycemia symptoms and self-treatment with 15 g rapid-acting carbohydrates.
Clinical Pearls
- Glimepiride produces inactive metabolites, unlike glyburide's active metabolites, reducing cumulative hypoglycemia risk especially in patients with renal impairment.
- Among sulfonylureas, glimepiride has the most evidence for cardiovascular safety and is often considered the preferred sulfonylurea when one is needed.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.