Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00881530.

Figure 1

Mean ± SE change from baseline in efficacy variables over 90 weeks in patients who received 10 mg empagliflozin, 25 mg empagliflozin, or metformin IR in study 1 or 10 mg empagliflozin, 25 mg empagliflozin, or sitagliptin as add-on to metformin in study 2 without rerandomization at the start of the extension trial. Changes in HbA_1c (A), changes in FPG (B), and changes in body weight (C) in patients on monotherapy (left panels) and on add-on to metformin therapy (right panels). Full analysis set, last-observation-carried-forward. Based on ANCOVA with treatment group, number of previously used antidiabetes medications as fixed effects, the corresponding baseline value of the end point under consideration as a covariate, and country as random effect. Boxes show mean change from baseline (95% CI) at week 78 of the extension trial (i.e., after 90 weeks’ treatment).