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.

Figures

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 HbA1c (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).