Effects of sotagliflozin added to insulin in patients with type 1 diabetes

Satish K. Garg, Robert R. Henry, Phillip Banks, John B. Buse, Melanie J. Davies, Gregory R. Fulcher, Paolo Pozzilli, Diane Gesty-Palmer, Pablo Lapuerta, Rafael Simó, Thomas Danne, Darren K McGuire, Jake A. Kushner, Anne Peters, Paul Strumph

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Abstract

BACKGROUND In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. METHODS In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin. RESULTS A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P=0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0% [21 patients] and 2.4% [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively). CONCLUSIONS Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035.).

Original languageEnglish (US)
Pages (from-to)2337-2348
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number24
DOIs
StatePublished - Dec 14 2017

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Type 1 Diabetes Mellitus
Insulin
Placebos
Diabetic Ketoacidosis
Glycosylated Hemoglobin A
Hypoglycemia
Blood Pressure
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
Weights and Measures
Therapeutics
Random Allocation
Least-Squares Analysis
Blood Glucose
Safety
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Garg, S. K., Henry, R. R., Banks, P., Buse, J. B., Davies, M. J., Fulcher, G. R., ... Strumph, P. (2017). Effects of sotagliflozin added to insulin in patients with type 1 diabetes. New England Journal of Medicine, 377(24), 2337-2348. https://doi.org/10.1056/NEJMoa1708337

Effects of sotagliflozin added to insulin in patients with type 1 diabetes. / Garg, Satish K.; Henry, Robert R.; Banks, Phillip; Buse, John B.; Davies, Melanie J.; Fulcher, Gregory R.; Pozzilli, Paolo; Gesty-Palmer, Diane; Lapuerta, Pablo; Simó, Rafael; Danne, Thomas; McGuire, Darren K; Kushner, Jake A.; Peters, Anne; Strumph, Paul.

In: New England Journal of Medicine, Vol. 377, No. 24, 14.12.2017, p. 2337-2348.

Research output: Contribution to journalArticle

Garg, SK, Henry, RR, Banks, P, Buse, JB, Davies, MJ, Fulcher, GR, Pozzilli, P, Gesty-Palmer, D, Lapuerta, P, Simó, R, Danne, T, McGuire, DK, Kushner, JA, Peters, A & Strumph, P 2017, 'Effects of sotagliflozin added to insulin in patients with type 1 diabetes', New England Journal of Medicine, vol. 377, no. 24, pp. 2337-2348. https://doi.org/10.1056/NEJMoa1708337
Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. New England Journal of Medicine. 2017 Dec 14;377(24):2337-2348. https://doi.org/10.1056/NEJMoa1708337
Garg, Satish K. ; Henry, Robert R. ; Banks, Phillip ; Buse, John B. ; Davies, Melanie J. ; Fulcher, Gregory R. ; Pozzilli, Paolo ; Gesty-Palmer, Diane ; Lapuerta, Pablo ; Simó, Rafael ; Danne, Thomas ; McGuire, Darren K ; Kushner, Jake A. ; Peters, Anne ; Strumph, Paul. / Effects of sotagliflozin added to insulin in patients with type 1 diabetes. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 24. pp. 2337-2348.
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abstract = "BACKGROUND In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. METHODS In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0{\%} at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin. RESULTS A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6{\%}] vs. 107 of 703 [15.2{\%}], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P=0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0{\%} [21 patients] and 2.4{\%} [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0{\%} [21 patients] and 0.6{\%} [4], respectively). CONCLUSIONS Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0{\%} with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035.).",
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T1 - Effects of sotagliflozin added to insulin in patients with type 1 diabetes

AU - Garg, Satish K.

AU - Henry, Robert R.

AU - Banks, Phillip

AU - Buse, John B.

AU - Davies, Melanie J.

AU - Fulcher, Gregory R.

AU - Pozzilli, Paolo

AU - Gesty-Palmer, Diane

AU - Lapuerta, Pablo

AU - Simó, Rafael

AU - Danne, Thomas

AU - McGuire, Darren K

AU - Kushner, Jake A.

AU - Peters, Anne

AU - Strumph, Paul

PY - 2017/12/14

Y1 - 2017/12/14

N2 - BACKGROUND In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. METHODS In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin. RESULTS A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P=0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0% [21 patients] and 2.4% [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively). CONCLUSIONS Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035.).

AB - BACKGROUND In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. METHODS In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin. RESULTS A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P=0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0% [21 patients] and 2.4% [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively). CONCLUSIONS Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035.).

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