• David R Powell, Brian Zambrowicz, Linda Morrow, Carine Beysen, Marcus Hompesch, Scott Turner, Marc Hellerstein, Phillip Banks, Paul Strumph, and Pablo Lapuerta.
• Lexicon Pharmaceuticals, Inc, The Woodlands, Texas.
• J. Clin. Endocrinol. Metab. 2020 Apr 1; 105 (4).

ContextThe effect of sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans.ObjectiveTo measure rate of appearance of oral glucose (RaO) using a dual glucose tracer method following standardized mixed meals taken after single sotagliflozin or canagliflozin doses.SettingClinical research organization.Design And ParticipantsIn a double-blind, 3-period crossover study (NCT01916863), 24 healthy participants were randomized to 2 cohorts of 12 participants. Within each cohort, participants were randomly assigned single oral doses of either sotagliflozin 400 mg, canagliflozin 300 mg, or placebo on each of test days 1, 8, and 15. On test days, Cohort 1 had breakfast containing [6,6-2H2] glucose 0.25 hours postdose and lunch containing [1-2H1] glucose 5.25 hours postdose; Cohort 2 had breakfast containing no labeled glucose 0.25 hours postdose and lunch containing [6,6-2H2] glucose 4.25 hours postdose. All participants received a 10- to 15-hour continuous [U-13C6] glucose infusion starting 5 hours before their first [6,6-2H2] glucose-containing meal.Main OutcomeRaO, postprandial glucose (PPG), and postprandial insulin.ResultsSotagliflozin and canagliflozin decreased area under the curve (AUC)0-1 hour and/or AUC0-2 hours for RaO, PPG, and insulin after breakfast and/or the 4.25-hour postdose lunch (P < .05 versus placebo). After the 5.25-hour postdose lunch, sotagliflozin lowered RaO AUC0-1 hour and PPG AUC0-5 hours versus both placebo and canagliflozin (P < .05).ConclusionsSotagliflozin delayed and blunted intestinal glucose absorption after meals, resulting in lower PPG and insulin levels, likely due to prolonged local inhibition of intestinal SGLT1 that persisted for ≥5 hours after dosing.© Endocrine Society 2019.

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