The mechanism of action of sodium-glucose co-transporter 2 inhibitors is similar to carbonic anhydrase inhibitors.

Abstract

Butler et al.,1 in their review about the poten-tial role of sodium–glucose co-transporter-2inhibitors (SGLT2i) in the treatment of heartfailure (HF), do not mention the carbonicanhydrase (CA) inhibitors, whose mechanismof action has remarkable similarities withSGLT2i.Although there are no studies in humans, 2it is established that around 30% of thefiltered Na+ is reabsorbed through theNa+/H+ isoform 3 (NHe3) exchanger, whichis located in the proximal convoluted tubule(PCT), whereas up to 15% of tubular Na+is reabsorbed through SGLT2 in situationsof hyperglycaemia. The SGLT2i inhibit boththe SGLT2 and the NHe3 exchangers thatshare the microdomain with SGLT2, 2 andthey have a natriuretic effect independentof the glycaemic level. 3 On the other hand,NHe3 is activated in HF and is involved in thestates of resistance to diuretics.