This study investigated the long-term efficacy and safety of empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes mellitus (T2DM). Of 666 patients treated with empagliflozin 10mg, empagliflozin 25mg or placebo once daily for 24 weeks, 472 patients (70.9%) were treated in a double-blind extension trial for ≥52 weeks. Pre-specified exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76. At week 76, adjusted mean differences versus placebo in change from baseline in HbA1c were −0.7% (−8mmol/mol) with empagliflozin 10mg or 25mg (both p<0.001), in weight were −1.8kg and −1.6kg with empagliflozin 10mg and 25mg, respectively (both p<0.001), and in systolic blood pressure (SBP) were −2.2mmHg with empagliflozin 10mg (p=0.021) and −2.1mmHg with empagliflozin 25mg (p=0.029). Sensitivity analyses provided consistent results for HbA1c and weight, but showed no significant difference between empagliflozin and placebo in change from baseline in SBP. Adverse events (AEs) were reported in 81.7%, 82.0% and 81.3% of patients on empagliflozin 10mg, 25mg and placebo, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9mmol/l and/or requiring assistance) were reported in 23.7%, 19.4% and 15.6% of patients on empagliflozin 10mg, 25mg and placebo, respectively; one patient each on empagliflozin 10mg and placebo required assistance. In conclusion, empagliflozin as add-on to metformin plus sulphonylurea for 76 weeks was well tolerated and led to sustained reductions in HbA1c and weight versus placebo.NCT01289990.