Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study

• DOI: 10.2337/dc18-0343
• Publication Date: 2018-06-24T20:15:11Z
• Authors: John B. Buse; Satish K. Garg; Julio Rosenstock; Timothy S. Bailey; Phillip Banks; Bruce W. Bode; Thomas Danne; Jake A. Kushner; Wendy S. Lane; Pablo Lapuerta; Darren K. McGuire; Anne L. Peters; John Reed; Sangeeta Sawhney; Paul Strumph
• Keywords: Adult; Glycated Hemoglobin; Male; Body Weight; Middle Aged; Hypoglycemia; Diabetic Ketoacidosis; 3. Good health; 03 medical and health sciences; Diabetes Mellitus, Type 1; Insulin Infusion Systems; 0302 clinical medicine; Double-Blind Method; North America; Weight Loss; Humans; Insulin; Drug Therapy, Combination; Female; Glycosides; Aged

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 inTandem1 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 400 mg (n = 262) after 6 weeks of insulin 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 −1.08 mmol/L for fasting plasma glucose, −4.32 kg for weight, and −15.63% for bolus insulin dose and −11.87% 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).