OBJECTIVE: To investigate the long-term safety and efficacy of empagliflozin, a 
sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients 
with type 2 diabetes.
RESEARCH DESIGN AND METHODS: In this randomized, open-label, 78-week extension 
study of two 12-week, blinded, dose-finding studies of empagliflozin 
(monotherapy and add-on to metformin) with open-label comparators, 272 patients 
received 10 mg empagliflozin (166 as add-on to metformin), 275 received 25 mg 
empagliflozin (166 as add-on to metformin), 56 patients received metformin, and 
56 patients received sitagliptin as add-on to metformin.
RESULTS: Changes from baseline in HbA1c at week 90 were -0.34 to -0.63% (-3.7 to 
-6.9 mmol/mol) with empagliflozin, -0.56% (-6.1 mmol/mol) with metformin, and 
-0.40% (-4.4 mmol/mol) with sitagliptin. Changes from baseline in weight at week 
90 were -2.2 to -4.0 kg with empagliflozin, -1.3 kg with metformin, and -0.4 kg 
with sitagliptin. Adverse events (AEs) were reported in 63.2-74.1% of patients 
on empagliflozin and 69.6% on metformin or sitagliptin; most AEs were mild or 
moderate in intensity. Hypoglycemic events were rare in all treatment groups, 
and none required assistance. AEs consistent with genital infections were 
reported in 3.0-5.5% of patients on empagliflozin, 1.8% on metformin, and none 
on sitagliptin. AEs consistent with urinary tract infections were reported in 
3.8-12.7% of patients on empagliflozin, 3.6% on metformin, and 12.5% on 
sitagliptin.
CONCLUSIONS: Long-term empagliflozin treatment provided sustained glycemic and 
weight control and was well tolerated with a low risk of hypoglycemia in 
patients with type 2 diabetes.