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

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). 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 (<i>n</i> = 93), sotagliflozin 200 mg (<i>n</i> = 89), or sotagliflozin 400 mg (<i>n</i> = 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. 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% (<i>P</i> = 0.026; +1.3/-0.1 h/day) for sotagliflozin 200 mg and +11.7%/-0.1% (<i>P</i> < 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; <i>P</i> = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 13 mg/dL; <i>P</i> < 0.001) with sotagliflozin 200 and 400 mg, respectively. 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.