Losartan vs Irbesartan
## Overview
Losartan and irbesartan are both ARBs used primarily for hypertension, diabetic nephropathy, and LV hypertension. Irbesartan is a non-prodrug with longer half-life and no uricosuric effect.
## Mechanism of Action
Both block AT1 receptors. Irbesartan is an insurmountable (non-competitive) AT1 blocker, meaning increasing angiotensin II concentrations cannot overcome its blockade — a pharmacodynamic advantage over surmountable ARBs like losartan.
## Pharmacokinetics
Irbesartan: no prodrug conversion, CYP2C9 metabolism (primarily), half-life ~11–15 h, bioavailability ~60–80%, renal and fecal elimination. Losartan: prodrug (CYP2C9 → E-3174), half-life of active metabolite ~9 h.
## Clinical Evidence
IDNT trial (irbesartan) demonstrated renoprotection in type 2 diabetic nephropathy independent of blood pressure lowering. IRMA-2 showed irbesartan reduced progression of microalbuminuria to macroalbuminuria. Losartan's RENAAL trial showed similar renal protection in diabetic nephropathy.
## Key Takeaways
- Irbesartan: insurmountable AT1 blockade, longer half-life, proven in diabetic nephropathy (IDNT)
- Losartan: surmountable AT1 blockade, uricosuric, less potent per mg
- Both used for diabetic nephropathy; irbesartan has additional non-competitive binding advantage
결론
Both are effective for hypertension and diabetic nephropathy. Irbesartan's insurmountable AT1 blockade and longer half-life may provide more consistent blood pressure control. Losartan is preferred in hyperuricemia/gout. For diabetic nephropathy, both are guideline-acceptable choices.