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Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption

CONTEXT: The effect of sotagliflozin (a dual sodium–glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans. OBJECTIVE: To measure rate of appearance of oral glucose (R(a)O) using a dual glucose tracer method following standardized mix...

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Autores principales: Powell, David R, Zambrowicz, Brian, Morrow, Linda, Beysen, Carine, Hompesch, Marcus, Turner, Scott, Hellerstein, Marc, Banks, Phillip, Strumph, Paul, Lapuerta, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067537/
https://www.ncbi.nlm.nih.gov/pubmed/31837264
http://dx.doi.org/10.1210/clinem/dgz258
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author Powell, David R
Zambrowicz, Brian
Morrow, Linda
Beysen, Carine
Hompesch, Marcus
Turner, Scott
Hellerstein, Marc
Banks, Phillip
Strumph, Paul
Lapuerta, Pablo
author_facet Powell, David R
Zambrowicz, Brian
Morrow, Linda
Beysen, Carine
Hompesch, Marcus
Turner, Scott
Hellerstein, Marc
Banks, Phillip
Strumph, Paul
Lapuerta, Pablo
author_sort Powell, David R
collection PubMed
description CONTEXT: The effect of sotagliflozin (a dual sodium–glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans. OBJECTIVE: To measure rate of appearance of oral glucose (R(a)O) using a dual glucose tracer method following standardized mixed meals taken after single sotagliflozin or canagliflozin doses. SETTING: Clinical research organization DESIGN AND PARTICIPANTS: In 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-(2)H(2)] glucose 0.25 hours postdose and lunch containing [1-(2)H(1)] glucose 5.25 hours postdose; Cohort 2 had breakfast containing no labeled glucose 0.25 hours postdose and lunch containing [6,6-(2)H(2)] glucose 4.25 hours postdose. All participants received a 10- to 15-hour continuous [U-(13)C(6)] glucose infusion starting 5 hours before their first [6,6-(2)H(2)] glucose-containing meal. MAIN OUTCOME: R(a)O, postprandial glucose (PPG), and postprandial insulin. RESULTS: Sotagliflozin and canagliflozin decreased area under the curve (AUC)(0–1 hour) and/or AUC(0–2 hours) for R(a)O, 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 R(a)O AUC(0–1 hour) and PPG AUC(0–5 hours) versus both placebo and canagliflozin (P < .05). CONCLUSIONS: Sotagliflozin 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.
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spelling pubmed-70675372020-03-18 Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption Powell, David R Zambrowicz, Brian Morrow, Linda Beysen, Carine Hompesch, Marcus Turner, Scott Hellerstein, Marc Banks, Phillip Strumph, Paul Lapuerta, Pablo J Clin Endocrinol Metab Online Only Articles CONTEXT: The effect of sotagliflozin (a dual sodium–glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans. OBJECTIVE: To measure rate of appearance of oral glucose (R(a)O) using a dual glucose tracer method following standardized mixed meals taken after single sotagliflozin or canagliflozin doses. SETTING: Clinical research organization DESIGN AND PARTICIPANTS: In 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-(2)H(2)] glucose 0.25 hours postdose and lunch containing [1-(2)H(1)] glucose 5.25 hours postdose; Cohort 2 had breakfast containing no labeled glucose 0.25 hours postdose and lunch containing [6,6-(2)H(2)] glucose 4.25 hours postdose. All participants received a 10- to 15-hour continuous [U-(13)C(6)] glucose infusion starting 5 hours before their first [6,6-(2)H(2)] glucose-containing meal. MAIN OUTCOME: R(a)O, postprandial glucose (PPG), and postprandial insulin. RESULTS: Sotagliflozin and canagliflozin decreased area under the curve (AUC)(0–1 hour) and/or AUC(0–2 hours) for R(a)O, 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 R(a)O AUC(0–1 hour) and PPG AUC(0–5 hours) versus both placebo and canagliflozin (P < .05). CONCLUSIONS: Sotagliflozin 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. Oxford University Press 2019-12-14 /pmc/articles/PMC7067537/ /pubmed/31837264 http://dx.doi.org/10.1210/clinem/dgz258 Text en © Endocrine Society 2019. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Online Only Articles
Powell, David R
Zambrowicz, Brian
Morrow, Linda
Beysen, Carine
Hompesch, Marcus
Turner, Scott
Hellerstein, Marc
Banks, Phillip
Strumph, Paul
Lapuerta, Pablo
Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title_full Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title_fullStr Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title_full_unstemmed Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title_short Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption
title_sort sotagliflozin decreases postprandial glucose and insulin concentrations by delaying intestinal glucose absorption
topic Online Only Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067537/
https://www.ncbi.nlm.nih.gov/pubmed/31837264
http://dx.doi.org/10.1210/clinem/dgz258
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