@article{d349711f09bd44f9985d707de74c5043,
title = "Improved time in range and glycemic variability with sotagliflozin in combination with insulin in adults with type 1 diabetes: A pooled analysis of 24-week continuous glucose monitoring data from the IntanDEM program",
abstract = "OBJECTIVE To evaluate effects of the dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibitor sotagliflozin in combination with insulin on glucose time in range (TIR) and glucose excursions, postprandial glucose (PPG), and other glycemic metrics in adults with type 1 diabetes using masked continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS Data sets from the inTandem1 (clinical trial reg. no. NCT02384941) and inTandem2 (clinical trial reg. no. NCT02421510) double-blind randomized trials evaluating sotagliflozin versus placebo in adults with type 1 diabetes treated with optimized insulin were pooled for analyses of masked CGM data from a subset of participants in each trial. The pooled cohort included patients randomized to receive placebo (n = 93), sotagliflozin 200 mg (n = 89), or sotagliflozin 400 mg (n = 96). The primary outcome was change from baseline to week 24 in glucose TIR (3.9–10.0 mmol/L [70–180 mg/dL]). Secondary end points included time below and above the target range and 2-h PPG level assessed after a standardized mixed meal. RESULTS Mean percentage of glucose TIR/percentage time spent at <3.9 mmol/L (<70 mg/dL) during week 24 was 51.6%/5.9%, 57.8%/5.5%, and 64.2%/5.5% with placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively, which corresponded to a placebo-adjusted change from a baseline of +5.4%/20.3% (P = 0.026; +1.3/20.1 h/day) for sotagliflozin 200 mg and +11.7%/20.1% (P < 0.001; +2.8/20.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 6 0.7 mmol/L (35 6 13 mg/dL; P = 0.004) and 2.8 6 0.7 mmol/L (50 6 13 mg/dL; P < 0.001) with sotagliflozin 200 and 400 mg, respectively. CONCLUSIONS Combined with optimized insulin in type 1 diabetes, sotagliflozin significantly increased glucose TIR without increasing time spent at <3.9 mmol/L and reduced PPG, thereby improving glycemic control.",
author = "Thomas Danne and Bertrand Cariou and Buse, {John B.} and Garg, {Satish K.} and Julio Rosenstock and Phillip Banks and Kushner, {Jake A.} and McGuire, {Darren K.} and Peters, {Anne L.} and Sangeeta Sawhney and Paul Strumph",
note = "Funding Information: Acknowledgments. The authors thank the inTandem1 and inTandem2 trial investigators, staff, and patients for their participation. The authors also thank the following employees of Lexicon Pharmaceuticals, Inc., for reviewing the manuscript: Diane Gesty-Palmer, David Powell, Lisa Sherman, and Kristi Boehm. In addition, the authors thank Amanda Justice, who provided medical writing and editorial support, which was funded by Lexicon Pharmaceuticals, Inc. Finally, theauthorsthankCovanceInc.(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 Pharmaceuticals, Inc., and Sanofi entered into a license agreement Funding Information: effective in November 2015 and are collaborating on the development and commercialization of sotagliflozin. J.B.B. is supported by a grant from the National Institutes of Health (UL1-TR-002489). T.D. has acted as consultant, advisory boardmember,andsteeringcommitteemember or speaker for Abbott, Medtronic, Roche, Lexicon Pharmaceuticals, Inc., Menarini, Boehringer In-gelheim, AstraZeneca, Novo Nordisk, Sanofi, Dexcom, and Eli Lilly and has received research grants from Abbott, AstraZeneca, Novo Nordisk, Medtronic, and Sanofi. B.C. has received research funding from Amgen, Pfizer, Sanofi, and Regen-eron Pharmaceuticals, Inc. and has served on scientific advisory boards and received honoraria or consulting fees from Abbott, Akcea, Amgen, AstraZeneca, Genfit, Pierre Fabre, Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, Regeneron, Sanofi, and Servier. J.B.B. has received contracted consulting fees, paid to his institution, and travel support from Adocia, AstraZeneca, Dexcom, Elcelyx Therapeutics, Eli Lilly, Intarcia Therapeutics, Lexicon Pharmaceuticals, Inc., Meta-vention, NovaTarg, Novo Nordisk, Sanofi, Sense-onics, and vTv Therapeutics; grant support from AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Lexicon Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Theracos, and vTv Therapeutics; holds stock options in Mellitus Health, PhaseBio, and Stability Health; is a consultant to Neurim-mune AG; and has served on the board of the AstraZeneca HealthCare Foundation. S.K.G. reports receiving grant support and travel support from Sanofi, Lexicon Pharmaceuticals, Inc., Novo Nordisk, MannKind, Roche Diagnostics, Zealand, Senseonics Inc., and Medtronic; research grants and advisory board fees from AstraZeneca; and grant support paid to his institution from Eli Lilly, Dexcom, and Johnson & Johnson. J.R. has served on scientific advisory boards and received honoraria or consulting fees from Eli Lilly, Sanofi, Novo Nordisk, Janssen, AstraZeneca, Boehringer In-gelheim, and Intarcia and has also received grants/research support from Merck, Pfizer, Sanofi, Novo Nordisk, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Genentech, Janssen, Lexicon Pharmaceuticals,Inc.,BoehringerIngelheim,and Intarcia. P.B. is employed by Lexicon Pharmaceuticals,Inc.J.A.K.servesasmedicaldirectorof McNair Interests, a private equity group with investments in type 1 diabetes and other chronic illnesses, and is also an advisor for Sanofi and Lexicon. D.K.M. has received consulting fees and fees for serving on a clinical trial executive committee from Applied Therapeutics, Boehringer Ingelheim, Sanofi US, Novo Nordisk, and AstraZeneca; consulting fees from Lilly USA and Metavant Sciences, Ltd.; 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 the steering committees for Lexicon Pharmaceuticals, Inc.; 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, Eli Lilly and Company, Livongo, MannKind, Medscape, Merck, Novo Nordisk, Omada Health, Sanofi, and Zafgen; is chair of the type 1 diabetes steering committee at Lexicon Pharmaceuticals, Inc.; has participated in a speaker{\textquoteright}s bureau for Novo Nordisk; and has received research funding from AstraZeneca, Dexcom, and MannKind. S.S. is employed by and holds stock in Lexicon Pharmaceuticals, Inc. P.S. owns stock in and was employed by Lexicon Pharmaceuticals, Inc. at the time the study was conducted and the manuscript was written and is now employed by Metavant Sciences, Ltd. No other potential conflicts of interest relevant to this article were reported. Author Contributions. T.D., J.A.K., D.K.M., and A.L.P. conceived and conducted the study, including acquisition, analysis, and interpretation of the data; participated in the drafting and critical revision of the manuscript; had full access to the data in the study; and had final responsibility for the decision to publish. B.C., J.B.B., S.K.G., and J.R. conducted the study, including acquisition, analysis, and interpretation of data; participated in the drafting and critical revision of the manuscript; had full access to the data in the study; and had final responsibility for the decision to publish. P.B. participated in the drafting and critical revision of the manuscript; conceived the study, including analysis and interpretation of data; contributed to the statistical design, analysis, and interpretation of data; oversaw the statistical analyses conducted by the independent statistician; reviewed the data quality prior to database lock; was involved in approving the protocol and its amendments; had full access to the data in the study; and had final responsibility for the decision to publish. S.S. conceived and conducted the study, including acquisition, analysis, and interpretation of the data; participated in the drafting and critical revision of the manuscript; reviewed the data quality prior to database lock; and had full access to the data in the study and final responsibility for the decision to publish. P.S. participated in the drafting and critical revision of the manuscript; conceived and conducted the study, including acquisition, analysis, and interpretation of data; reviewed the data quality prior to database lock; was involved in approving the protocol and its amendments; had full access to the data in the study; and had final responsibility for the decision to publish. T.D. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study (the inTandem1 and inTandem2 pooled CGM results) were presented in abstract form at the 78th Scientific Sessions of the American Diabetes Association, Orlando, FL, 22–26 June 2018. Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",
year = "2019",
month = may,
day = "1",
doi = "10.2337/dc18-2149",
language = "English (US)",
volume = "42",
pages = "919--930",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "5",
}