Table 2

Changes in CGM values and 2-h PPG at week 24*

Placebo (n = 93)Sotagliflozin 200 mg (n = 89)Sotagliflozin 400 mg (n = 96)
Time in target range, 3.9–10.0 mmol/L (70–180 mg/dL)
 Percentage time 3.9–10.0 mmol/L (70–180 mg/dL)
  Patients, n616372
  Mean baseline ± SD52.3 ± 13.852.2 ± 15.350.7 ± 14.8
  Mean week 24 ± SD51.6 ± 14.757.8 ± 15.964.2 ± 14.0
  Change from baseline, LSM ± SE (95% CI; P value)−1.3 ± 1.8 (−4.8 to 2.3; 0.49)4.1 ± 1.8 (0.5–7.6; 0.024)10.5 ± 1.7 (7.1–13.8; <0.001)
  Difference from placebo ± SE (95% CI; P value)5.4 ± 2.4 (0.6–10.1; 0.026)11.7 ± 2.3 (7.1–16.3; <0.001)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE1.3 ± 0.62.8 ± 0.6
Time in hyperglycemic range
 Percentage time >10.0 mmol/L (>180 mg/dL)
  Patients, n616372
  Mean baseline ± SD41.9 ± 15.441.9 ± 16.744.0 ± 17.1
  Mean week 24 ± SD42.6 ± 16.936.7 ± 16.830.3 ± 14.5
  Change from baseline, LSM ± SE (95% CI; P value)1.2 ± 2.0 (−2.7 to 5.1; 0.54)−3.8 ± 2.0 (−7.7 to 0.1; 0.055)−10.5 ± 1.9 (−14.2 to −6.8; <0.001)
  Difference from placebo ± SE (95% CI; P value)−5.0 ± 2.6 (−10.2 to 0.1; 0.055)−11.8 ± 2.5 (−16.7 to −6.8; <0.001)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−1.2 ± 0.6−2.8 ± 0.6
 Percentage time >13.9 mmol/L (>250 mg/dL)
  Patients, n616372
  Mean baseline ± SD17.9 ± 12.418.6 ± 13.017.6 ± 12.2
  Mean week 24 ± SD17.4 ± 12.613.3 ± 12.78.6 ± 8.2
  Change from baseline, LSM ± SE (95% CI; P value)0.2 ± 1.4 (−2.5 to 2.9; 0.90)−3.5 ± 1.4 (−6.2 to −0.8; 0.012)−7.5 ± 1.3 (−10.0 to −5.0; <0.001)
  Difference from placebo ± SE (95% CI; P value)−3.7 ± 1.8 (−7.3 to −0.1; 0.045)−7.7 ± 1.8 (−11.2 to −4.2; <0.001)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−0.9 ± 0.4−1.9 ± 0.4
Time in hypoglycemic ranges
 Percentage time <3.9 mmol/L (<70 mg/dL)
  Patients, n616372
  Mean baseline ± SD5.8 ± 5.35.9 ± 5.65.4 ± 6.1
  Mean week 24 ± SD5.9 ± 5.25.5 ± 5.65.5 ± 5.2
  Change from baseline, LSM ± SE (95% CI; P value)0.1 ± 0.7 (−1.2 to 1.4; 0.84)−0.2 ± 0.7 (−1.5 to 1.1; 0.76)0.1 ± 0.6 (−1.2 to 1.3; 0.92)
  Difference from placebo ± SE (95% CI; P value)−0.3 ± 0.9 (−2.0 to 1.4; 0.70)−0.1 ± 0.8 (−1.7 to 1.6; 0.93)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−0.1 ± 0.2−0.02 ± 0.2
 Percentage time <3.9 mmol/L (<70 mg/dL) during nocturnal period (0000–0559 h)
  Patients, n716875
  Mean baseline ± SD8.2 ± 11.07.4 ± 9.87.6 ± 10.5
  Change from baseline, LSM ± SE (95% CI; P value)−1.4 ± 1.2 (−3.8 to 1.0; 0.25)−0.6 ± 1.3 (−3.0 to 1.9; 0.66)1.0 ± 1.2 (−1.4 to 3.3; 0.43)
  Difference from placebo ± SE (95% CI; P value)0.9 ± 1.6 (−2.3 to 4.1; 0.59)2.4 ± 1.6 (−0.7 to 5.5; 0.13)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE0.2 ± 0.40.6 ± 0.4
 Percentage time <3.9 mmol/L (<70 mg/dL) during diurnal period (0600–2359 h)
  Patients, n616371
  Mean baseline ± SD5.3 ± 5.15.6 ± 5.44.6 ± 5.1
  Change from baseline, LSM ± SE (95% CI; P value)0.6 ± 0.6 (−0.6 to 1.8; 0.35)−0.07 ± 0.6 (−1.3 to 1.1; 0.91)0.2 ± 0.6 (−1.0 to 1.3; 0.79)
  Difference from placebo ± SE (95% CI; P value)−0.6 ± 0.8 (−2.2 to 0.9; 0.42)−0.4 ± 0.8 (−1.9 to 1.1; 0.59)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−0.1 ± 0.2−0.1 ± 0.2
 Percentage time <3.0 mmol/L (<55 mg/dL)
  Patients, n616372
  Mean baseline ± SD2.4 ± 3.02.4 ± 3.72.3 ± 4.0
  Mean week 24 ± SD2.4 ± 3.22.1 ± 3.11.8 ± 2.6
  Change from baseline, LSM ± SE (95% CI; P value)−0.1 ± 0.4 (−0.8 to 0.7; 0.88)−0.2 ± 0.4 (−1.0 to 0.5; 0.57)−0.5 ± 0.4 (−1.2 to 0.2; 0.16)
  Difference from placebo ± SE (95% CI; P value)−0.2 ± 0.5 (−1.1 to 0.8; 0.75)−0.4 ± 0.5 (−1.4 to 0.5; 0.36)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−0.04 ± 0.1−0.1 ± 0.1
 Percentage time <3.0 mmol/L (<55 mg/dL) during nocturnal period (00:00–05:59 h)
  Patients, n716875
  Mean baseline ± SD4.3 ± 7.33.3 ± 6.84.0 ± 7.3
  Change from baseline, LSM ± SE (95% CI; P value)−0.8 ± 0.8 (−2.4 to 0.8; 0.35)−0.6 ± 0.8 (−2.3 to 1.0; 0.44)−0.2 ± 0.8 (−1.8 to 1.3; 0.78)
  Difference from placebo ± SE (95% CI; P value)0.1 ± 1.1 (−2.0 to 2.2; 0.91)0.5 ± 1.0 (−1.5 to 2.6; 0.61)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE0.02 ± 0.30.1 ± 0.3
 Percentage time <3.0 mmol/L (<55 mg/dL) during diurnal period (0600–2359 h)
  Patients, n616371
  Mean baseline ± SD1.9 ± 2.62.1 ± 3.51.7 ± 3.0
  Change from baseline, LSM ± SE (95% CI; P value)0.3 ± 0.3 (−0.3 to 0.9; 0.38)−0.1 ± 0.3 (−0.8 to 0.5; 0.71)−0.3 ± 0.3 (−0.9 to 0.3; 0.37)
  Difference from placebo ± SE (95% CI; P value)−0.4 ± 0.4 (−1.2 to 0.4; 0.33)−0.6 ± 0.4 (−1.4 to 0.2; 0.17)
  Difference from placebo in hours per day corresponding to percentage time per day ± SE−0.1 ± 0.1−0.1 ± 0.1
Glycemic instability
 AUC >10.0 mmol/L (>180 mg/dL), mmol/L (mg/dL) × minutes/1,000
  Patients, n616372
  Mean baseline ± SD2.4 ± 1.5 (43.6 ± 27.8)2.5 ± 1.7 (45.1 ± 30.2)2.4 ± 1.5 (44.0 ± 27.7)
  Change from baseline, LSM ± SE (95% CI; P value)0.1 ± 0.2 (1.3 ± 3.2) (−0.3 to 0.4 [−4.9 to 7.5]; 0.68)−0.4 ± 0.2 (−7.1 ± 3.2) (−0.7 to −0.1 [−13.3 to −0.9]; 0.024)−0.9 ± 0.2 (−16.4 ± 3.0) (−1.2 to −0.6 [−22.2 to −10.6]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−0.5 ± 0.2 (−8.4 ± 4.2) (−0.9 to −0.01 [−16.7 to −0.2]; 0.045)−1.0 ± 0.2 (−17.7 ± 4.1) (−1.4 to −0.5 [−25.7 to −9.7]; <0.001)
 AUC >13.9 mmol/L (>250 mg/dL), mmol/L (mg/dL) × minutes/1,000
  Patients, n616372
  Mean baseline ± SD0.8 ± 0.8 (14.7 ± 14.5)0.9 ± 0.9 (16.0 ± 16.3)0.8 ± 0.8 (14.0 ± 14.5)
  Change from baseline, LSM ± SE (95% CI; P value)0.03 ± 0.1 (0.6 ± 1.7) (−0.1 to 0.2 [−2.7 to 3.8]; 0.73)−0.2 ± 0.1 (−3.0 ± 1.6) (−0.3 to 0.01 [−6.3 to 0.2]; 0.07)−0.4 ± 0.1 (−6.3 ± 1.5) (−0.5 to −0.2 [−9.4 to −3.3]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−0.2 ± 0.1 (−3.6 ± 2.2) (−0.4 to 0.04 [−7.9 to 0.7]; 0.10)−0.4 ± 0.1 (−6.9 ± 2.1) (−0.6 to −0.1 [−11.1 to −2.7]; 0.001)
 AUC <3.9 (<70 mg/dL), mmol/L (mg/dL) × minutes/1,000
  Patients, n616372
  Mean baseline ± SD0.1 ± 0.1 (1.2 ± 1.4)0.1 ± 0.1 (1.2 ± 1.6)0.1 ± 0.1 (1.1 ± 1.7)
  Change from baseline, LSM ± SE (95% CI; P value)−0.002 ± 0.01 (−0.04 ± 0.2) (−0.02 to 0.02 [−0.4 to 0.3]; 0.81)−0.006 ± 0.01 (−0.1 ± 0.2) (−0.02 to 0.01 [−0.4 to 0.2]; 0.57)−0.01 ± 0.01 (−0.2 ± 0.2) (−0.03 to 0.01 [−0.4 to 0.2]; 0.35)
  Difference from placebo ± SE (95% CI; P value)−0.006 ± 0.01 (−0.1 ± 0.2) (−0.03 to 0.02 [−0.5 to 0.4]; 0.81)−0.006 ± 0.01 (−0.1 ± 0.2) (−0.03 to 0.02 [−0.5 to 0.3]; 0.61)
 AUC <3.0 mmol/L (<55 mg/dL), mmol/L (mg/dL) × minutes/1,000
  Patients, n616372
  Mean baseline ± SD0.02 ± 0.03 (0.3 ± 0.5)0.02 ± 0.04 (0.3 ± 0.7)0.02 ± 0.04 (0.3 ± 0.7)
  Change from baseline, LSM ± SE (95% CI; P value)−0.006 ± 0.006 (−0.1 ± 0.1) (−0.01 to 0.006 [−0.2 to 0.1]; 0.33)−0.006 ± 0.006 (−0.1 ± 0.1) (−0.01 to 0.006 [−0.2 to 0.1]; 0.26)−0.006 ± 0.006 (−0.1 ± 0.1) (−0.01 to 0.001 [−0.2 to 0.02]; 0.10)
  Difference from placebo ± SE (95% CI; P value)−0.0006 ± 0.006 (−0.01 ± 0.1) (−0.01 to 0.01 [−0.2 to 0.1]; 0.91)−0.002 ± 0.006 (−0.03 ± 0.1) (−0.01 to 0.006 [−0.2 to 0.1]; 0.66)
PPG
 2-h PPG, mmol/L (mg/dL)§
  Patients, n (per-protocol population)575962
  Mean baseline ± SD12.9 ± 5.1 (232 ± 93)12.3 ± 5.4 (221 ± 96)11.4 ± 5.1 (205 ± 91)
  Change from baseline, LSM ± SE (95% CI; P value)−0.2 ± 0.6 (−3.6 ± 10.4) (−1.3 to 0.9 [−24.2 to 16.9]; 0.73)−2.1 ± 0.6 (−38.3 ± 10.5) (−3.3 to −1.0 [−59.0 to −17.6]; <0.001)−3.0 ± 0.6 (−53.3 ± 10.1) (−4.1 to −1.9 [−73.2 to −33.4]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−1.9 ± 0.7 (−34.6 ± 13.2) (−3.4 to −0.5 [−60.6 to −8.6]; 0.009)−2.8 ± 0.7 (−49.7 ± 13.1) (−4.2 to −1.3 [−75.5 to −23.9]; <0.001)
Glycemic variability
 CV, %
  No. patients616372
  Mean baseline ± SD37.7 ± 5.937.9 ± 7.335.8 ± 7.4
  Change from baseline, LSM ± SE (95% CI; P value)−1.0 ± 0.9 (−2.7 to 0.8; 0.27)−2.5 ± 0.9 (−4.2 to −0.7; 0.005)−2.0 ± 0.8 (−3.7 to −0.4; 0.016)
  Difference from placebo ± SE (95% CI; P value)−1.5 ± 1.2 (−3.8 to 0.8; 0.20)−1.0 ± 1.1 (−3.3 to 1.2; 0.36)
 SD, mmol/L (mg/dL)
  Patients, n616372
  Mean baseline ± SD3.6 ± 0.8 (65 ± 15)3.7 ± 0.8 (66 ± 14)3.4 ± 0.8 (62 ± 14)
  Change from baseline, LSM ± SE (95% CI; P value)−0.1 ± 0.1 (−1.5 ± 1.7) (−0.3 to 0.1 [−4.8 to 1.9]; 0.40)−0.3 ± 0.1 (−6.0 ± 1.7) (−0.5 to −0.2 [−9.4 to −2.7]; <0.001)−0.5 ± 0.1 (−8.2 ± 1.6) (−0.6 to −0.3 [−11.4 to −5.1]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−0.3 ± 0.1 (−4.6 ± 2.3) (−0.5 to −0.01 [−9.0 to −0.2]; 0.042)−0.4 ± 0.1 (−6.8 ± 2.2) (−0.6 to −0.1 [−11.1 to −2.5]; 0.002)
 Mean daily glucose, mmol/L (mg/dL)
  Patients, n616372
  Mean baseline ± SD9.7 ± 1.7 (175 ± 31)9.8 ± 1.8 (176 ± 33)9.9 ± 1.8 (178 ± 32)
  Change from baseline, LSM ± SE (95% CI; P value)0.1 ± 0.2 (2.0 ± 3.6) (−0.3 to 0.5 [−5.0 to 9.1]; 0.57)−0.3 ± 0.2 (−5.9 ± 3.6) (−0.7 to 0.1 [−12.9 to 1.1]; 0.10)−0.9 ± 0.2 (−16.9 ± 3.4) (−1.3 to −0.6 [−23.5 to −10.3]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−0.4 ± 0.3 (−7.9 ± 4.7) (−1.0 to 0.1 [−17.2 to 1.3]; 0.09)−1.1 ± 0.3 (−18.9 ± 4.6) (−1.6 to −0.6 [−27.9 to −9.9]; <0.001)
 MAGE, mmol/L (mg/dL)
  Patients, n616372
  Mean baseline ± SD9.2 ± 2.0 (166 ± 35)9.1 ± 1.9 (163 ± 34)8.8 ± 2.0 (158 ± 36)
  Change from baseline, LSM ± SE (95% CI; P value)−0.2 ± 0.2 (−3.0 ± 4.2) (−0.6 to 0.3 [−11.3 to 5.4]; 0.48)−0.9 ± 0.2 (−15.7 ± 4.2) (−1.3 to −0.4 [−24.0 to −7.4]; <0.001)−1.4 ± 0.2 (−25.1 ± 3.9) (−1.8 to −1.0 [−32.8 to −17.3]; <0.001)
  Difference from placebo ± SE (95% CI; P value)−0.7 ± 0.3 (−12.7 ± 5.5) (−1.3 to −0.1 [−23.6 to −1.8]; 0.022)−1.2 ± 0.3 (−22.1 ± 5.4) (−1.9 to −0.7 [−32.7 to −11.5]; <0.001)
CGM hypoglycemic events
 Hypoglycemic events per patient per day, <3.9 mmol/L (<70 mg/dL)
  Patients, n616372
  Mean baseline ± SD1.1 ± 0.81.1 ± 0.70.9 ± 0.7
  Change from baseline, LSM ± SE (95% CI; P value)0.03 ± 0.1 (−0.2 to 0.2; 0.73)−0.2 ± 0.1 (−0.4 to 0.03; 0.11)−0.002 ± 0.1 (−0.2 to 0.2; 0.98)
  Difference from placebo ± SE (95% CI; P value)−0.2 ± 0.1 (−0.5 to 0.1; 0.15)−0.04 ± 0.1 (−0.3 to 0.2; 0.78)
 Hypoglycemic events per patient per day, <3.0 mmol/L (<55 mg/dL)
  Patients, n616372
  Mean baseline ± SD0.5 ± 0.50.4 ± 0.50.4 ± 0.4
  Change from baseline, LSM ± SE (95% CI; P value)0.1 ± 0.1 (−0.03 to 0.2; 0.14)0.003 ± 0.1 (−0.1 to 0.1; 0.96)−0.04 ± 0.1 (−0.2 to 0.1; 0.44)
  Difference from placebo ± SE (95% CI; P value)−0.1 ± 0.1 (−0.3 to 0.1; 0.28)−0.1 ± 0.1 (−0.3 to 0.02; 0.09)
  • LSM, least squares mean.

  • *Conducted in a subgroup of patients who underwent blinded CGM with a Dexcom G4 monitor (Dexcom Inc.) during specified 1-week intervals throughout the first 24 weeks.

  • †Included in 2017 international consensus on use of CGM (3). The consensus group identified hypoglycemia cutoffs as follows: level 1, <3.9–3.0 mmol/L (<70–54 mg/dL); level 2, <3.0 mmol/L (<54 mg/dL).

  • ‡Assuming 100% daily CGM data were available for analysis, 1.0% of daily CGM time = 0.24 h.

  • §To assess the change in PPG under standardized conditions, the per-protocol population was selected; 2-h plasma PPG values were obtained after a standardized mixed meal.

  • ‖A CGM hypoglycemic event was defined by CGM sensor values of at least 10 continuous minutes below the thresholds of 3.9 mmol/L (70 mg/dL) or 3.0 mmol/L (55 mg/dL).