Improved Glucose Control With Weight Loss, Lower Insulin Doses, and No Increased Hypoglycemia With Empagliflozin Added to Titrated Multiple Daily Injections of Insulin in Obese Inadequately Controlled Type 2 Diabetes

OBJECTIVE We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin +/- metformin (mean HbA(1c) 8.3% [67 mmol/mol]; BMI 34.8 kg/m(2); insulin dose 92 international units/day) were randomized and treated with once-daily empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189), or placebo (n = 188) for 52 weeks. Insulin dose was to remain stable in weeks 1-18, adjusted to meet glucose targets in weeks 19-40, then stable in weeks 41-52. The primary end point was change from baseline in HbA(1c) at week 18. Secondary end points were changes from baseline in insulin dose, weight, and HbA(1c) at week 52. RESULTS Adjusted mean +/- SE changes from baseline in HbA(1c) were -0.50 +/- 0.05%(-5.56 +/- 0.5 mmol/mol) for placebo versus -0.94 +/- 0.05% (-10.3 +/- 0.5 mmol/mol) and -1.02 +/- 0.05% (-11.1 +/- 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin 25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions with insulin titration resulted in changes from baseline in HbA(1c) of 20.81 +/- 0.08%(-8.9 +/- 0.9 mmol/mol), -1.18 +/- 0.08%(-12.9 +/- 0.9 mmol/mol), and -1.27 +/- 0.08%(-13.9 +/- 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively, and final HbA(1c) of 7.5% (58 mmol/mol), 7.2% (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA(1c) < 7% (<53 mmol/mol) with empagliflozin (31-42%) versus placebo (21%; both P < 0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (-9 to -11 international units/day) and weight (-2.4 to -2.5 kg) versus placebo (all P < 0.01) at week 52. CONCLUSIONS In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.