Adults with type 2 diabetes who had participated in one of two 12-week studies of empagliflozin (Boehringer Ingelheim, Eli Lilly) were treated for an additional 78 weeks with empagliflozin. Those treated with empagliflozin 1 mg, 5 mg or 50 mg or placebo in the first trial, were randomly assigned to empagliflozin at 10 mg or 25 mg alone or as an add-on to metformin. Patients treated with empagliflozin 10 mg or 25 mg, metformin alone or sitagliptin as an add-on to metformin continued the same treatment course.
At week 90, compared with metformin, empagliflozin at both the 10 mg and 25 mg doses was associated with reductions in average HbA1c levels (-0.56% vs. -0.34% and -0.47%), fasting plasma glucose levels (-26 mg/dL vs. -30.4 mg/dL and -27.8 mg/dL) and body weight (-1.28 kg vs. -2.24 kg and -2.61 kg).
As an add-on to metformin, empagliflozin was superior to sitagliptin in reducing HbA1c levels (-0.34% for 10 mg; -0.63% for 25 mg vs. -0.40%), fasting plasma glucose levels (-21.3 mg/dL for 10 mg; -31.8 mg/dL for 25 mg vs. -15.6 mg/dL) and body weight (-3.14 kg for 10 mg; -4.03 kg for 25 mg vs. -0.41 kg).
Both doses of empagliflozin were well-tolerated. When administered for at least 78 weeks and up to 90 weeks, 63.2% to 74.1% of patients on empagliflozin and 69.6% of those taking metformin alone or sitagliptin plus metformin experienced adverse events. Ninety percent of these events were mild or moderate.
The rate of hypoglycemic events was lower with empagliflozin (between 0.9% and 3.6%) compared with metformin alone (7.1%) and sitagliptin (5.4%). The rate of adverse events associated with urinary tract infections was similar among groups: 3.8% to 12.7% for empagliflozin; 3.6% for metformin alone and 12.5% for sitagliptin. Adverse events associated with genital infections occurred in 3% to 5.5% of those on empagliflozin; 1.8% of those on metformin alone and none of the patients on sitagliptin.
Empagliflozin is currently in phase 3 clinical development, with a planned enrollment of 14,500 patients.
This was a phase 2b open-label extension study.
Woerle HJ. Abstract #49-LB. Presented at: the American Diabetes Association's 72nd Scientific Sessions; June 8-12, 2012; Philadelphia.