PURPOSE: Oral agents are needed that improve glycemic control without increasing 
hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may 
meet this need, because this compound lowers blood glucose through the 
insulin-independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. 
We examined the effect of sotagliflozin on glycemic control and rate of 
hypoglycemia measurements in T1D mice maintained on a low daily insulin dose, 
and compared these results to those from mice maintained in better glycemic 
control with a higher daily insulin dose alone.
MATERIALS AND METHODS: Nonobese diabetes-prone mice with 
cyclophosphamide-induced T1D were randomized to receive one of four daily 
treatments: 0.2 U insulin/vehicle, 0.05 U insulin/vehicle, 0.05 U insulin/2 
mg/kg sotagliflozin or 0.05 U insulin/30 mg/kg sotagliflozin. Insulin was 
delivered subcutaneously by micro-osmotic pump; the day after pump implantation, 
mice received their first of 22 once-daily oral doses of sotagliflozin or 
vehicle. Glycemic control was monitored by measuring fed blood glucose and 
hemoglobin A1c levels.
RESULTS: Blood glucose levels decreased rapidly and comparably in the 0.05 U 
insulin/sotagliflozin-treated groups and the 0.2 U insulin/vehicle group 
compared to the 0.05 U insulin/vehicle group, which had significantly higher 
levels than the other three groups from day 2 through day 23. A1c levels were 
also significantly higher in the 0.05 U insulin/vehicle group compared to the 
other three groups on day 23. Importantly, the 0.2 U insulin/vehicle group had, 
out of 100 blood glucose measurements, 13 that were <70 mg/dL compared to one of 
290 for the other three groups combined.
CONCLUSION: Sotagliflozin significantly improved glycemic control, without 
increasing the rate of hypoglycemia measurements, in diabetic mice maintained on 
a low insulin dose. This sotagliflozin-mediated improvement in glycemic control 
was comparable to that achieved by raising the insulin dose alone, but was not 
accompanied by the increased rate of hypoglycemia measurements observed with the 
higher insulin dose.