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).

Patients inadequately controlled on MDI insulin ± metformin (mean HbA_1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m²; 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.

Adjusted mean ± SE changes from baseline in HbA_1c were −0.50 ± 0.05% (−5.5 ± 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 −0.81 ± 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.

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.