Thomas Danne1, Bertrand Cariou2, John B Buse3, Satish K Garg4, Julio Rosenstock5, Phillip Banks6, Jake A Kushner7, Darren K McGuire8, Anne L Peters9, Sangeeta Sawhney6, Paul Strumph6. 1. Department of Diabetes, Endocrinology, and Clinical Research, Children's and Youth Hospital Auf der Bult, Hannover Medical School, Hannover, Germany danne@hka.de. 2. L'institut du thorax, Department of Endocrinology, CIC 1413 INSERM, CHU Nantes, Nantes, France. 3. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC. 4. Department of Medicine and Pediatrics, Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO. 5. Dallas Diabetes Research Center at Medical City, Dallas, TX. 6. Lexicon Pharmaceuticals, Inc., The Woodlands, TX. 7. Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. 8. Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX. 9. Keck School of Medicine of the University of Southern California, Los Angeles, CA.
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%/-0.3% (P = 0.026; +1.3/-0.1 h/day) for sotagliflozin 200 mg and +11.7%/-0.1% (P < 0.001; +2.8/-0.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 ± 0.7 mmol/L (35 ± 13 mg/dL; P = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 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.
RCT Entities:
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%/-0.3% (P = 0.026; +1.3/-0.1 h/day) for sotagliflozin 200 mg and +11.7%/-0.1% (P < 0.001; +2.8/-0.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 ± 0.7 mmol/L (35 ± 13 mg/dL; P = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 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.
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