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Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes

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posted on 2018-03-14, 14:27 authored by Satish K. Garg, Robert R. Henry, Phillip Banks, John B. Buse, Melanie J. Davies, Gregory R. Fulcher, Paulo Pozzilli, Diane Gesty-Palmer, Pablo Lapuerta, Rafael Simó, Thomas Danne, Darren K. McGuire, Jake A. Kushner, Anne Peters, Paul Strumph
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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Citation

New England Journal of Medicine, 2017, 377, pp. 2337-2348

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Diabetes Research Centre

Version

  • VoR (Version of Record)

Published in

New England Journal of Medicine

Publisher

Massachusetts Medical Society

issn

0028-4793

eissn

1533-4406

Copyright date

2017

Available date

2018-03-14

Publisher version

http://www.nejm.org/doi/10.1056/NEJMoa1708337

Language

en

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