TY - JOUR
T1 - Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes
T2 - The North American in Tandem1 study
AU - Buse, John B.
AU - Garg, Satish K.
AU - Rosenstock, Julio
AU - Bailey, Timothy S.
AU - Banks, Phillip
AU - Bode, Bruce W.
AU - Danne, Thomas
AU - Kushner, Jake A.
AU - Lane, Wendy S.
AU - Lapuerta, Pablo
AU - McGuire, Darren K.
AU - Peters, Anne L.
AU - Reed, John
AU - Sawhney, Sangeeta
AU - Strumph, Paul
N1 - Funding Information:
Acknowledgments. The authors thank the inTandem1 trial investigators, staff, and patients for their participation and the following contributors for reviewing the manuscript: Roger Davies, Diane Gesty-Palmer, David Powell, and Kristi Boehm (Lexicon Pharmaceuticals, Inc., Woodlands, TX). Amanda Justice (independent consultant, Brooklyn, NY) provided medical writing and editorial support, which was funded by Lexicon Pharmaceuticals, Inc. The authors thank Covance, Inc. (Princeton, NJ), for providing the operational execution and medical monitoring of this study and Cenduit, LLC (Durham, NC), for visualization of CGM data. Funding and Duality of Interest. This study was supported and conducted by Lexicon Pharmaceuticals, Inc. Lexicon and Sanofi entered a license agreement effective November 2015 and are collaborating on the development and commercialization of sotagliflozin. J.B.B. received support from the National Institutes of Health National Center for Advancing Translational Sciences through Grant Award Number UL1TR002489. J.B.B. reports receiving grant support, travel support, and consulting fees paid to his institution from Eli Lilly, GI Dynamics, Merck, AstraZeneca, Sanofi, Intarcia Therapeutics, Lexicon, Orexigen, Takeda, and Novo Nordisk; travel support and consulting fees paid to his institution from Elcelyx Therapeutics, Metavention, vTv Therapeutics, Dance Biopharm, and Adocia; consulting fees paid to his institution from Dexcom, Fractyl, Senseonics, Shenzen HighTide, and NovaTarg; grant support from Medtronic MiniMed, Johnson & Johnson, Boehringer Ingelheim, GlaxoSmithKline, Scion NeuroStim, Theracos, and Bayer; stock options and consulting fees paid to his institution from PhaseBio Pharmaceuticals; stock options from Insulin Algorithms; and travel support and serving on the board of AstraZeneca HealthCare Foundation. S.K.G. reports receiving grant support and travel support from Sanofi, Lexicon, Novo Nordisk, MannKind, Roche Diagnostics, Senseonics, and Medtronic and grant support paid to his institution from Eli Lilly, Dexcom, and Johnson & Johnson. J.Ro. has served on scientific advisory boards and received honoraria or consulting fees from Eli Lilly, Sanofi, Novo Nordisk, Janssen, AstraZeneca, Boehringer Ingelheim, and Intarcia and has received grants/research support from Merck, Pfizer, Sanofi, Novo Nordisk, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Genentech, Janssen, Lexicon, Boehringer Ingelheim, and Intarcia. T.S.B. reports receiving research support from Abbott, Ambra, Ascensia, Becton Dickinson, Boehringer Ingelheim, Calibra, Companion Medical, Dexcom, GlySens, Lexicon, Eli Lilly, MannKind, Medtronic, Novo Nordisk, Sanofi, Sen-seonics, Versartis, and Xeris; consulting honoraria from AstraZeneca, Ascensia, Becton Dickinson, Calibra,EliLilly,Intarcia,Medtronic,NovoNordisk, and Sanofi; and speaking honoraria from Abbott, Insulet, EliLilly,Medtronic,NovoNordisk, and Sanofi. P.B., P.L., S.S., and P.S. are employed by Lexicon, and S.S. holds stock in Lexicon. B.W.B. reports stock ownership in Aseko and the receipt of consulting fees from Adocia, Intarcia, Janssen, Medtronic, MannKind, Novo Nordisk, and Sanofi and speakers’ bureau fees from AstraZeneca, Lilly/Boehringer Ingelheim, Janssen, Medtronic, MannKind, Novo Nordisk, and Sanofi; in addition, his employer (Atlanta Diabetes Associates) has received grant and research support from Abbott, Becton Dickinson, Dexcom, Diasome, GlaxoSmithKline, Janssen, Lexicon, Lilly/Boehringer Ingelheim, Medtronic, the National Institutes of Health, Novo Nordisk, Sanofi, and Senseonics. T.D. has acted as consultant, advisory board member, or speaker for Abbott, Medtronic, Roche, Lexicon, Menarini, Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Sanofi, Dexcom, and Eli Lilly and has received research grants from Abbott, AstraZeneca, Novo Nordisk, Medtronic, and Sanofi.J.A.K. serves on the type 1 diabetes steering committee for Lexicon and as an advisor for Sanofi and Know Foods. W.S.L. has received honoraria for speaking for Novo Nordisk, Insulet, and Dexcom and for advisory board participation for Novo Nordisk, Insulet, Intarcia, and Sanofi. D.K.M. has received consulting fees and fees for serving on clinical trial executive committees from Boehringer Ingelheim, Sanofi U.S., Novo Nordisk, and AstraZeneca; consulting fees from Lilly USA; advisory board fees and fees for serving on a clinical trial executive committee from Merck Sharp & Dohme; fees for serving on a data monitoring committee from Janssen Research and Development and GlaxoSmithKline; fees for chairing an executive committee from Lexicon; and fees for serving on a clinical trial executive or steering committee from Eisai and Esperion. A.L.P. has participated on advisory boards for Abbott Diabetes Care, Becton Dickinson, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, Lexicon,
Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The in Tandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400mg(n =262) after6 weeks ofinsulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks. RESULTS: From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P < 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were 21.08 mmol/L for fasting plasma glucose, 24.32 kg for weight, and 215.63% for bolus insulin dose and 211.87% for basal insulin dose (all P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo. CONCLUSIONS: In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).
AB - OBJECTIVE: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The in Tandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400mg(n =262) after6 weeks ofinsulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks. RESULTS: From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P < 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were 21.08 mmol/L for fasting plasma glucose, 24.32 kg for weight, and 215.63% for bolus insulin dose and 211.87% for basal insulin dose (all P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo. CONCLUSIONS: In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).
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U2 - 10.2337/dc18-0343
DO - 10.2337/dc18-0343
M3 - Article
C2 - 29937430
AN - SCOPUS:85052656308
SN - 0149-5992
VL - 41
SP - 1970
EP - 1980
JO - Diabetes care
JF - Diabetes care
IS - 9
ER -