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%/-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.

© 2019 by the American Diabetes Association.

Figures

Figure 1

Time spent in glycemic ranges of 10.0 mmol/L (180 mg/dL) among patients monitored with blinded CGM. Time values were calculated by multiplying values for the percentage of time spent in specified ranges (Table 2) by 0.24 (assumes 100% data capture) to determine the number of hours, and the resulting right-of-decimal values by 60 to determine the number of minutes (e.g., the baseline percentage of TIR of 3.9–10.0 mmol/L in the placebo group was 52.3% × 0.24 = 12.552 h; 0.552 × 60 = 33 min). PBO, placebo.

Figure 2

Average day represented by a 24-h CGM tracing consisting of interstitial glucose readings collected every 5 min from the week prior to the week 24 visit. The figure shows data collected from midnight (0000 h). The actual start time for 24-h readings may vary for each patient. Solid lines represent mean values from each treatment group (light purple = placebo [n = 93]; light blue = sotagliflozin 200 mg [n = 89]; dark blue = sotagliflozin 400 mg [n = 96]); shaded areas represent ± 1 SEM. Top of the target CGM range = 10.0 mmol/L (180 mg/dL). The decline in mean glucose value from 12:00 to 6:00 a.m. in patients treated with sotagliflozin was not associated with a significant increase in nocturnal hypoglycemia. Ambulatory glucose profiles (AGPs) for CGM data collected from each treatment group in the week prior to week 24 appear in the Supplementary Data. Patient and aggregate visualizations of CGM data, as well as AGPs, were generated by Cenduit, LLC (Durham, NC) and any reproductions must acknowledge Cenduit.