Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial

Claire Baker, Suman Wason, Phillip Banks, Sangeeta Sawhney, Anna Chang, Thomas Danne, Diane Gesty-Palmer, Jake A. Kushner, Darren K McGuire, Frank Mikell, Mark O'Neill, Anne L. Peters, Paul Strumph

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D). Materials and methods: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). Results: From a mean baseline of 8.0% ± 0.8% (full study population), placebo-adjusted LSM HbA1c decreased by 0.3% (P =.07), 0.5% (P <.001) and 0.4% (P =.006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo-adjusted PPG decreased by 22.2 mg/dL (P =.28), 28.7 mg/dL (P =.16) and 50.2 mg/dL (P =.013), UGE increased by 41.8 g/d (P =.006), 57.7 g/d (P <.001) and 70.5 g/d (P <.001), and weight decreased by 1.3 kg (P =.038), 2.4 kg (P <.001) and 2.6 kg (P <.001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. Conclusions: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).

Original languageEnglish (US)
JournalDiabetes, Obesity and Metabolism
DOIs
StatePublished - Jan 1 2019

Fingerprint

Type 1 Diabetes Mellitus
Glucose
Placebos
Diabetic Ketoacidosis
Least-Squares Analysis
Hypoglycemia
Weights and Measures
Sodium-Glucose Transporter 1
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Insulin
Symporters
Glycosylated Hemoglobin A

Keywords

  • glycaemic control
  • insulin therapy
  • phase 2 study
  • randomized trial
  • SGLT2 inhibitor
  • type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks : The inTandem4 trial. / Baker, Claire; Wason, Suman; Banks, Phillip; Sawhney, Sangeeta; Chang, Anna; Danne, Thomas; Gesty-Palmer, Diane; Kushner, Jake A.; McGuire, Darren K; Mikell, Frank; O'Neill, Mark; Peters, Anne L.; Strumph, Paul.

In: Diabetes, Obesity and Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

Baker, C, Wason, S, Banks, P, Sawhney, S, Chang, A, Danne, T, Gesty-Palmer, D, Kushner, JA, McGuire, DK, Mikell, F, O'Neill, M, Peters, AL & Strumph, P 2019, 'Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial', Diabetes, Obesity and Metabolism. https://doi.org/10.1111/dom.13825
Baker, Claire ; Wason, Suman ; Banks, Phillip ; Sawhney, Sangeeta ; Chang, Anna ; Danne, Thomas ; Gesty-Palmer, Diane ; Kushner, Jake A. ; McGuire, Darren K ; Mikell, Frank ; O'Neill, Mark ; Peters, Anne L. ; Strumph, Paul. / Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks : The inTandem4 trial. In: Diabetes, Obesity and Metabolism. 2019.
@article{5293896b513a40238cb4f3426871ed41,
title = "Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial",
abstract = "Aims: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D). Materials and methods: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5{\%} HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). Results: From a mean baseline of 8.0{\%} ± 0.8{\%} (full study population), placebo-adjusted LSM HbA1c decreased by 0.3{\%} (P =.07), 0.5{\%} (P <.001) and 0.4{\%} (P =.006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3{\%}, 37.1{\%}, 80.0{\%} and 65.7{\%} of participants achieved an HbA1c reduction ≥0.5{\%}. Placebo-adjusted PPG decreased by 22.2 mg/dL (P =.28), 28.7 mg/dL (P =.16) and 50.2 mg/dL (P =.013), UGE increased by 41.8 g/d (P =.006), 57.7 g/d (P <.001) and 70.5 g/d (P <.001), and weight decreased by 1.3 kg (P =.038), 2.4 kg (P <.001) and 2.6 kg (P <.001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. Conclusions: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).",
keywords = "glycaemic control, insulin therapy, phase 2 study, randomized trial, SGLT2 inhibitor, type 1 diabetes",
author = "Claire Baker and Suman Wason and Phillip Banks and Sangeeta Sawhney and Anna Chang and Thomas Danne and Diane Gesty-Palmer and Kushner, {Jake A.} and McGuire, {Darren K} and Frank Mikell and Mark O'Neill and Peters, {Anne L.} and Paul Strumph",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/dom.13825",
language = "English (US)",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks

T2 - The inTandem4 trial

AU - Baker, Claire

AU - Wason, Suman

AU - Banks, Phillip

AU - Sawhney, Sangeeta

AU - Chang, Anna

AU - Danne, Thomas

AU - Gesty-Palmer, Diane

AU - Kushner, Jake A.

AU - McGuire, Darren K

AU - Mikell, Frank

AU - O'Neill, Mark

AU - Peters, Anne L.

AU - Strumph, Paul

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aims: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D). Materials and methods: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). Results: From a mean baseline of 8.0% ± 0.8% (full study population), placebo-adjusted LSM HbA1c decreased by 0.3% (P =.07), 0.5% (P <.001) and 0.4% (P =.006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo-adjusted PPG decreased by 22.2 mg/dL (P =.28), 28.7 mg/dL (P =.16) and 50.2 mg/dL (P =.013), UGE increased by 41.8 g/d (P =.006), 57.7 g/d (P <.001) and 70.5 g/d (P <.001), and weight decreased by 1.3 kg (P =.038), 2.4 kg (P <.001) and 2.6 kg (P <.001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. Conclusions: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).

AB - Aims: To assess the dose-related effects of sotagliflozin, a novel dual inhibitor of sodium-glucose co-transporters-1 and -2, in type 1 diabetes (T1D). Materials and methods: In this 12-week, multicentre, randomized, double-blind, placebo-controlled dose-ranging trial, adults with T1D were randomized to once-daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2-hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). Results: From a mean baseline of 8.0% ± 0.8% (full study population), placebo-adjusted LSM HbA1c decreased by 0.3% (P =.07), 0.5% (P <.001) and 0.4% (P =.006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo-adjusted PPG decreased by 22.2 mg/dL (P =.28), 28.7 mg/dL (P =.16) and 50.2 mg/dL (P =.013), UGE increased by 41.8 g/d (P =.006), 57.7 g/d (P <.001) and 70.5 g/d (P <.001), and weight decreased by 1.3 kg (P =.038), 2.4 kg (P <.001) and 2.6 kg (P <.001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. Conclusions: Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).

KW - glycaemic control

KW - insulin therapy

KW - phase 2 study

KW - randomized trial

KW - SGLT2 inhibitor

KW - type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85070069138&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070069138&partnerID=8YFLogxK

U2 - 10.1111/dom.13825

DO - 10.1111/dom.13825

M3 - Article

C2 - 31264767

AN - SCOPUS:85070069138

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

ER -