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Sotagliflozin (Sota) inhibits sodium glucose cotransporter 2 (SGLT2; IC50=1.8 nM) and SGLT1 (IC50=36 nM). In humans, Sota improves glycemic control in part by increasing urinary glucose excretion via renal SGLT2 inhibition. Sota also lowers postprandial glucose (PPG), likely by inhibiting intestinal SGLT1 to delay the rate of appearance of oral glucose (RaO). To test the hypothesis that Sota delays SGLT1-mediated RaO, we performed a randomized, 3-period crossover study comparing effects of single doses of placebo (Pbo), Sota (400 mg) and canagliflozin (Cana, 300 mg), an SGLT2 inhibitor (IC50=4.2 nM) that inhibits SGLT1 (IC50=663 nM) with lower potency than Sota, on RaO using a dual-glucose tracer method in two cohorts of 12 healthy subjects each; plasma glucose, insulin and additional pharmacodynamic parameters were also evaluated.
