Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial

Abstract

Objective: To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes.

Research design and methods: Patients inadequately controlled on metformin and sulfonylurea (HbA1c ≥7 to ≤10%) were randomized and treated with once-daily empagliflozin 10 mg (n = 225), empagliflozin 25 mg (n = 216), or placebo (n = 225) for 24 weeks. The primary end point was change from baseline in HbA1c at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24.

Results: At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.17% (0.05) for placebo vs. -0.82% (0.05) and -0.77% (0.05) for empagliflozin 10 and 25 mg, respectively (both P < 0.001). Empagliflozin significantly reduced MDG, weight, and systolic (but not diastolic) blood pressure versus placebo. Adverse events were reported in 62.7, 67.9, and 64.1% of patients on placebo and empagliflozin 10 and 25 mg, respectively. Events consistent with urinary tract infection were reported in 8.0, 10.3, and 8.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 13.3, 18.0, and 17.5%, respectively; males: 2.7, 2.7, and 0%, respectively). Events consistent with genital infection were reported in 0.9, 2.7, and 2.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 0.9, 4.5, and 3.9%, respectively; males: 0.9% in each group).

Conclusions: Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic control, weight, and systolic blood pressure and were well tolerated.

Trial registration: ClinicalTrials.gov NCT01159600.

Figure 1

Study flow.

Figure 2

Effect of empagliflozin on efficacy parameters. A: HbA_1c over time in randomized groups (mixed model repeated measures, FAS, and OC). B: Change from baseline in HbA_1c at week 24 in randomized groups (ANCOVA, FAS, and LOCF imputation). C: HbA_1c over time in the open-label treatment group (OC and descriptive statistics). D: Change from baseline in MDG at week 24 in randomized groups (ANCOVA, FAS, and OC). E: Change from baseline in weight at week 24 (ANCOVA, FAS, and LOCF). F: Change from baseline in SBP at week 24 (ANCOVA, FAS, and LOCF). G: Change from baseline in DBP at week 24 (ANCOVA, FAS, and LOCF). Data are adjusted mean (SE) for randomized groups and mean (SE) for open-label treatment group. *P < 0.001 vs. placebo; †P = 0.032 vs. placebo; ‡P = 0.005 vs. placebo; §P = 0.557 vs. placebo; ¶P = 0.534 vs. placebo.

Figure 2

Effect of empagliflozin on efficacy parameters. A: HbA_1c over time in randomized groups (mixed model repeated measures, FAS, and OC). B: Change from baseline in HbA_1c at week 24 in randomized groups (ANCOVA, FAS, and LOCF imputation). C: HbA_1c over time in the open-label treatment group (OC and descriptive statistics). D: Change from baseline in MDG at week 24 in randomized groups (ANCOVA, FAS, and OC). E: Change from baseline in weight at week 24 (ANCOVA, FAS, and LOCF). F: Change from baseline in SBP at week 24 (ANCOVA, FAS, and LOCF). G: Change from baseline in DBP at week 24 (ANCOVA, FAS, and LOCF). Data are adjusted mean (SE) for randomized groups and mean (SE) for open-label treatment group. *P < 0.001 vs. placebo; †P = 0.032 vs. placebo; ‡P = 0.005 vs. placebo; §P = 0.557 vs. placebo; ¶P = 0.534 vs. placebo.