Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes
Article Figures & Tables
Figures
- Figure 1
Study design.
Tables
- Table 1
Demographic characteristics (intent-to-treat population)
Patient characteristics Placebo (N = 17) Sotagliflozin (N = 16) Age (years), median (range) 34.0 (21, 57) 45.5 (21, 55) Sex, n (%) Female 9 (53) 8 (50) Male 8 (47) 8 (50) Race, n (%) White/Caucasian 14 (82) 16 (100) Asian 2 (12) 0 Other 1 (6) 0 Weight (kg), median (range) 72.7 (55.3, 104.6) 74.2 (55.6, 107.9) BMI (kg/m2), mean (SD) 26.2 (3.0) 27.1 (3.1) Duration of diabetes (years), median (range) 18.5 (4.7, 40.8) 16.8 (3.4, 42.9) HbA1c (%), mean (SD) 7.98 (0.51) 7.94 (0.55) HbA1c (mmol/mol), mean (SD) 62.83 (5.66) 63.38 (6.04) FPG (mmol/L), mean (SD) 8.89 (3.96) 9.45 (3.45) Seated systolic BP (mmHg), mean (SD) 119.8 (7.0) 118.1 (9.2) Serum sodium (mmol/L), mean (SD) 138.24 (3.75) 137.63 (2.45) Serum creatinine (µmol/L), mean (SD) 76.11 (9.86) 76.94 (11.82) Serum BUN (mmol/L), mean (SD) 4.68 (0.99) 4.96 (1.02) Hematocrit, mean (SD) 41.94 (4.87) 41.63 (4.86) Insulin therapy, n (%) MDI 5 (29) 6 (38) CSII 12 (71) 10 (63) Total daily insulin (IU/kg), mean 0.60 0.60 Daily insulin, ratio of bolus/total 0.45 0.49 BP, blood pressure.
- Table 2
Overall summary of results
Placebo (N = 17) Sotagliflozin (N = 16) P Efficacy HbA1c change from baseline (%) −0.06 −0.55* 0.002 FPG change from baseline assessed at day 29 (mg/dL) 39.0 −18.6 0.15 Daily bolus insulin change from baseline assessed at days 3–27 (%) −6.4 −32.0* 0.007 Daily basal insulin change from baseline assessed at days 3–27 (%) 0.2 −2.4 0.53 Total daily insulin change from baseline assessed at days 3–27 (%) −0.7 −15.3* 0.029 Mean body weight change from baseline assessed at day 29 (kg) 0.5 −1.7* 0.005 Postmeal urinary glucose (g/3 h) at day 29† 9.2 29.1 0.025 Postmeal plasma glucose AUC (mg ⋅ h/dL over 3 h) at day 29† 761 595 0.005 PYY postmeal AUC change from baseline assessed at day 29 (pmol/L ⋅ h over 3 h) −0.7 6.0* 0.018 Seated systolic blood pressure change from baseline assessed at day 29 (mmHg) −3.9 −4.9 0.45 Safety Patients with any TEAE (%) 12 (71) 14 (88) N/A Patients with SAE (both with DKA‡) 0 2 N/A Hypoglycemic events (SMBG ≤70 mg/dL, baseline–day 36) 354 304 N/A Documented symptomatic hypoglycemia (SMBG ≤70 mg/dL, baseline–day 36) 185 162 N/A Asymptomatic hypoglycemia (SMBG ≤70 mg/dL, baseline–day 36) 117 80 N/A SH 0 0 N/A Hypoglycemia (SMBG ≤70 mg/dL, PPD) change from baseline at days 3–27 −0.4* −0.7* 0.77 Hypoglycemia (CGM ≥10 continuous min <70 mg/dL, PPD) change from baseline assessed at days 3–27 −0.15 −0.09 0.75 Laboratory values associated with volume status Serum sodium (mmol/L), change from baseline at day 29 (day 36) −1.00 (−0.53) −0.50 (1.50) N/A Serum creatinine (µmol/L), change from baseline at day 29 (day 36) −0.53 (1.53) 2.63 (0.63) N/A Serum BUN (mmol/L), change from baseline at day 29 (day 36) 0.41 (0.11) 1.02 (−0.41) N/A Hematocrit, change from baseline at day 29 (day 36) −1.4 (0) 2.1 (1.5) N/A For laboratory values, change from baseline was assessed at day 29, the last day of therapy, and day 36, 1 week off therapy, unless otherwise specified. N/A, not applicable; SAE, serious adverse event.
↵*P < 0.05, change from baseline.
↵†Day 1 is not a true “baseline”; therefore, P values are calculated from two-sample t tests using the observed means.
↵‡Both were assessed as due to insulin pump and deemed not drug related. Bold values are statistically significant.
- Table 3
Summary of CGM and CGM-derived results and prespecified insulin dose analysis
Placebo (N = 17) Sotagliflozin (N = 16) P Baseline Treatment Change from baseline value [%] Baseline Treatment Change from baseline value [%] CGM mean daily glucose (mg/dL) 160.6 (25.9) 170.3 (24.0) 5.9 [NC] 163.6 (38.7) 148.8 (18.0)* −14.0 [NC] 0.010 CGM hypoglycemia events/patient/day (≥10 continuous min <70 mg/dL) 1.09 (1.01) 0.90 (0.47) −0.2 [NC] 1.06 (0.59) 0.95 (0.41) −0.1 [NC] 0.75 CGM % time in ranges (mg/dL) <70 8.5 (9.5) 5.8 (4.7) −2.3 [NC] 7.9 (7.3) 6.7 (5.0) −1.5 [NC] 0.80 70–180 55.9 (12.1) 54.0 (12.0) −0.2 [NC] 56.4 (15.6) 68.2 (12.1)* 11.6 [NC] 0.003 >180 35.6 (14.4) 40.2 (13.7) 2.5 [NC] 35.7 (18.3) 25.0 (11.2)* −10.1 [NC] 0.002 >250 12.0 (9.3) 14.1 (7.9) 1.1 [NC] 15.3 (14.8) 6.7 (6.6)* −7.9 [NC] 0.008 CGM variability measures SD (mg/dL) 57.2 (13.9) 58.8 (9.6) 1.2 [NC] 60.5 (16.5) 50.0 (12.2)* −8.9 [NC] 0.022 Coefficient of variation 35.6 (8.8) 35.4 (5.2) 0.3 [NC] 37.4 (5.2) 33.7 (6.0) −2.9 [NC] 0.41 MAGE 135.5 (34.9) 145.5 (25.6) 7.5 [NC] 145.5 (39.5) 120.8 (30.5)* −20.0 [NC] 0.041 HBGI 8.7 (3.7) 9.7 (3.7) 0.5 [NC] 9.2 (6.5) 6.2 (3.1)* −2.9 [NC] 0.006 LBGI 2.2 (2.2) 1.5 (1.1)* −0.6 [NC] 1.9 (1.5) 1.8 (1.2) −0.2 [NC] 0.61 Insulin dose data Total daily bolus (primary) 20.9 (14.0) 18.8 (11.2) −2.1 [−6.4] 23.0 (11.6) 15.4 (9.2) −7.3 [−32.0] 0.007 Total daily basal 26.1 (9.4) 25.9 (9.3) −0.2 [0.2] 27.1 (7.1) 26.6 (8.7) −0.5 [−2.4] 0.53 Total daily (basal + bolus) 45.9 (17.5) 44.4 (15.5) −1.5 [−0.7] 47.0 (17.9) 37.6 (15.3) −7.6 [−15.3] 0.029 Breakfast bolus 4.8 (4.1) 4.4 (2.9) — [13.6] 5.6 (3.6) 3.4 (2.0) — [−28.4] 0.046 Lunch bolus 5.6 (4.8) 5.0 (3.9) — [7.1] 6.4 (3.9) 4.4 (2.7) — [−25.9] 0.08 Dinner bolus 6.2 (5.7) 5.8 (4.2) — [39.3] 7.2 (4.1) 5.3 (3.4) — [−23.8] 0.052 Data are mean (SD) unless otherwise indicated. Arithmetic change from baseline is shown; P values are from least squares mean analyses of change from baseline scores (absolute and % change). The baseline analysis period consists of days −6 to −2, and the treatment analysis period consists of days 3–27. LBGI, low blood glucose index; NC, not calculated.
↵*P < 0.05, change from baseline. Bold values are statistically significant.
In this Issue
July 2015, 38(7)
Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes
