Losartan Differences – A Deep Dive on ARBs

Angiotensin II receptor blockers (ARBs) are widely used in managing hypertension, heart failure, chronic kidney disease (CKD), and diabetic nephropathy. While these agents share a common mechanism—blocking the angiotensin II type 1 (AT₁) receptor—not all ARBs are created equal. As healthcare professionals, understanding the nuanced differences can guide therapy optimization, especially in patients with comorbidities or specific pharmacokinetic needs. In this blog post, I will highlight important losartan differences when comparing this medication to other ARBs

Losartan and Gout? Uricosuric Action

One of the most unique losartan differences is uricosuric properties (excellent board exam nugget). It inhibits urate transporter 1 (URAT1), lowering serum uric acid levels—a useful feature in patients with gout or hyperuricemia. Would I select this medication specifically for this purpose over a medication like allopurinol? Of course not, allopurinol has much stronger evidence and experience in practice. However, if you have a gout patient with moderate to high uric acid levels AND hypertension, it makes a lot of sense to utilize a medication like losartan. It really makes a lot of sense when you compare it to commonly used thiazide diuretics which can raise uric acid levels.

Prodrug and Metabolism

Losartan is different among ARBs because it is a prodrug. After oral administration, it is metabolized by CYP2C9 and CYP3A4 to a more potent metabolite with longer activity at the AT₁ receptor. If you have patients taking CYP inhibitors that affect 2C9 and 3A4 conversion to the active metabolite may be reduced and it is possible to have lower efficacy.

Losartan Frequency

Losartan has a shorter half-life (~2 hours for the parent drug, 6–9 hours for the active metabolite) compared to other ARBs like telmisartan or olmesartan. Because of this, many patients may require twice daily dosing. In practice, I don’t see twice daily dosing done a lot in practice but see it occasionally. If you are utilizing once-daily losartan, it might not be a bad idea to get blood pressures at varying times of the day to ensure that it is adequately controlled on once-daily dosing. This is a bit of a disadvantage to losartan compared to other longer-acting ARBs that may provide better 24-hour blood pressure coverage in patients needing a once-daily medication.

What else would you add to this list of losartan differences when comparing it to other ARBs?

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