Dapagliflozin with losartan but not olmesartan has an add-on protective effect in experimental Alport syndrome

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and angiotensin receptor blockers (ARBs) each have renoprotective effects in chronic kidney diseases, including Alport syndrome. Here, we investigated the combination of SGLT2i dapagliflozin and ARBs with different antiproteinuric strength - losartan (weak) and olmesartan (strong) - in Col4a5 G5X Alport mice. Dapagliflozin enhanced the renoprotective effect of losartan but not of olmesartan. Olmesartan alone suppressed the decline in renal function and prolonged survival similarly to losartan plus dapagliflozin. These findings suggest that the add-on effectiveness of dapagliflozin varies depending on the ARB, and that their combination needs careful evaluation for maximum benefit.