Sodium-Glucose Cotransporter 2 Inhibition and Glycemic Control in Type 1 Diabetes: Results of an 8-Week Open-Label Proof-of-Concept Trial

OBJECTIVE: Adjunctive-to-insulin therapy with sodium-glucose cotransporter 2 (SGLT2) inhibition may improve glycemic control in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: We evaluated the glycemic efficacy and safety of empagliflozin 25 mg daily in 40 patients treated for 8 weeks in a single-arm open-label proof-of-concept trial (NCT01392560). RESULTS: Mean A1C decreased from 8.0 ± 0.9% (64 ± 10 mmol/mol) to 7.6 ± 0.9% (60 ± 10 mmol/mol) (P < 0.0001), fasting glucose from 9.0 ± 4.3 to 7.0 ± 3.2 mmol/L (P = 0.008), symptomatic hypoglycemia (<3.0 mmol/L) from 0.12 to 0.04 events per patient per day (P = 0.0004), and daily insulin dose from 54.7 ± 20.4 to 45.8 ± 18.8 units/day (P < 0.0001). Mean urinary excretion of glucose increased from 19 ± 19 to 134 ± 61 g/day (P < 0.0001). Weight decreased from 72.6 ± 12.7 to 70.0 ± 12.3 kg (P < 0.0001), and waist circumference decreased from 82.9 ± 8.7 to 79.1 ± 8.0 cm (P < 0.0001). CONCLUSIONS: This proof-of-concept study strongly supports a randomized clinical trial of adjunctive-to-insulin empagliflozin in patients with T1D.