Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes

OBJECTIVE To assess the safety and efficacy of dual sodium–glucose cotransporter(SGLT) 1 and SGLT2 inhibition with sotagliflozinas adjunct therapy to insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment. RESULTS In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% ( P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring ( CGM) of 148.8 mg/dL (8.3 mmol/L) ( P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) ( P = 0.002) in HbA 1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA 1c . The percentage of time in target glucose range 70–180 mg/dL (3.9–10.0 mmol/L) increased from baseline with sotagliflozincompared with placebo, to 68.2% vs. 54.0% ( P = 0.003), while the percentage of time in hyperglycemic range >180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% ( P = 0.002), for sotagliflozinand placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozincompared with a 0.5 kg gain ( P = 0.005) in the placebo group. CONCLUSIONS As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozinimproved glycemic control and the CGMprofile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.