TY - JOUR
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
N1 - Funding Information:
Supported by Lexicon Pharmaceuticals. (Lexicon Pharmaceuticals and Sanofi entered a license agreement, effective November 2015, and are collaborating on the development and commercialization of sotagliflozin.) Dr. Garg reports receiving grant support and travel support from Sanofi, Lexicon, Novo Nordisk, Mannkind, and Medtronic and grant support paid to his institution from Eli Lilly, Dexcom, and Johnson & Johnson; Dr. Henry, receiving consulting fees and advisory board fees from AstraZeneca, Boehringer Ingel-heim, Intarcia, Johnson & Johnson, and Sanofi, consulting fees from Alere, Ionis, REMD, and Ligand, advisory board fees from Elcelyx, and grant support from AstaReal, Eli Lilly, Hitachi, Lexicon, and Viacyte; Dr. Banks, being employed by and holding equity in Lexicon; Dr. Buse, receiving grant support, travel support, and consulting fees paid to his institution from Eli Lilly, GI Dynamics, Merck, AstraZeneca, Sanofi, Intarcia, Lexicon, Orexi-gen, Takeda, and Novo Nordisk, travel support and consulting fees paid to his institution from Elcylex, Metavention, vTv Therapeutics, Dance Biopharm, and Adocia, consulting fees paid to his institution from Dexcom, Fractyl, Shenzhen HighTide, and NovaTarg, grant support from Medtronic, Johnson & Johnson, Boehringer Ingelheim, GlaxoSmithKline, Scion NeuroStim, Theracos, and Bayer, stock options and consulting fees paid to his institution from PhaseBio, and stock options from Insulin Algorithms and receiving travel support from and serving on the board of AstraZeneca HealthCare Foundation; Dr. Davies, receiving grant support, consulting fees, lecture fees, and advisory board fees from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingel-heim, and Janssen, consulting fees, lecture fees, and advisory board fees from Merck Sharp & Dohme and AstraZeneca, advisory board fees from Servier, and lecture fees from Mitsubishi Tanabe Pharma and Takeda; Dr. Pozzilli, receiving grant support and lecture fees from Eli Lilly, GlaxoSmithKline, and Sanofi, grant support from AstraZeneca and Lexicon, and lecture fees from Medtronic; Dr. Gesty-Palmer, being employed by and holding equity in Lexicon; Dr. Lapuerta, being employed by and holding equity in Lexicon; Dr. Simó, receiving grant support and advisory board fees from Novo Nordisk and serving as an investigator on a clinical trial for Sanofi; Dr. Danne, receiving grant support, lecture fees, and advisory board fees from Sanofi and Eli Lilly, grant support and lecture fees from Abbott, AstraZeneca, Novo Nordisk, and Medtronic, lecture fees from Roche, Menarini, and Dexcom, and advisory board fees from Boehringer Ingel-heim; Dr. McGuire, receiving consulting fees and fees for serving on a clinical trial executive committee from Boehringer Ingel-heim, Sanofi, Novo Nordisk, and AstraZeneca, consulting fees from Eli Lilly, advisory board fees and fees for serving on a clinical trial executive committee from Merck Sharp & Dohme, fees for serving on a data and safety monitoring committee from Janssen Research and Development and GlaxoSmithKline, fees for serving as chair on a clinical trial from Lexicon, and fees for serving on a clinical trial executive or steering committee from Eisai and Esperion; Dr. Kushner, receiving grant support from Merck and consulting fees from Virta Health; Dr. Peters, receiving advisory board fees from Becton Dickinson, Bigfoot Biomedical, Boehringer Ingelheim, Omada Health, Science 37, Merck, Sanofi, and Lexicon, advisory board fees and lecture fees from Eli Lilly and Novo Nordisk, lecture fees from Medscape, donated supplies for a study from Dexcom, and grant support and advisory board fees from Janssen and serving on an unpaid advisory board for Livongo; and Dr. Strumph, being employed by Lexicon. No other potential conflict of interest relevant to this article was reported.
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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U2 - 10.1056/NEJMoa1708337
DO - 10.1056/NEJMoa1708337
M3 - Article
C2 - 28899222
AN - SCOPUS:85031780039
VL - 377
SP - 2337
EP - 2348
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 24
ER -