Dual sodium-glucose cotransporter (SGLT) 1/2 versus pure SGLT2 inhibitors: two distinct drug categories or one class with multiple faces?

In large cardiovascular outcome trials, dual inhibitors have shown a unique efficacy profile in terms of reducing glycemia in patients with severe renal impairment and decreasing the risk of atherosclerotic outcomes. These features do not characterize selective SGLT2 inhibitors and could be attributed to the parallel inhibition of SGLT1. The increased risk of diarrhea and severe hypoglycemia observed only with dual inhibitors is probably related to their action in the gut and brain, respectively. However, differences in populations included in various studies should be considered when attempting to translate their findings into clinical practice; therefore, head-to-head trials are needed to shed more light on this issue and provide clear guidance to clinicians.