• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

Empagliflozin is superior to glimepiride as an add-on treatment option for patients with type 2 diabetes mellitus (T2DM) who have not achieved good glycemic control on metformin, according to results from the Efficacy and Safety of Empagliflozin (BI 10773) With Metformin in Patients With Type 2 Diabetes trial [Ridderstråle M et al. Lancet Diabetes Endocrinol. 2014], announced lead investigator Martin Ridderstråle, MD, Steno Diabetes Center, Gentofte, Denmark.

Metformin represents traditional first-line therapy for patients with T2DM, but there is no consensus regarding optimal second-line treatment. According to Prof Ridderstråle, empagliflozin is a selective sodium-glucose cotransporter 2 inhibitor, a new class of drugs for the management of T2DM, while glimepiride is a sulfonylurea.

This phase 3 double-blind study aimed to compare the efficacy and safety of empagliflozin and glimepiride as second-line therapy in patients with T2DM who are not adequately controlled on metformin. The study included patients > 18 years with a body mass index ≤ 45 kg/m² and with HbA_1c levels between 7% and 10% who were on a stable background therapy of metformin for ≥ 12 weeks before randomization. The investigators excluded subjects with an estimated glomerular filtration rate < 60 mL/min/1.73 m² during screening or placebo run-in.

The researchers randomized participants (n = 1549) in a 1:1 ratio to oral empagliflozin (25 mg, QD) or oral glimepiride (1 to 4 mg, QD) as add-on to metformin for 104 weeks. The primary end point was the change from baseline in HbA_1c levels at weeks 52 and 104 and included noninferiority and superiority criteria.

From baseline to 104 weeks, patients treated with empagliflozin had significantly greater reductions in mean HbA_1c levels when compared with patients treated with glimepiride. Empagliflozin was noninferior to glimepiride at baseline and 104 weeks. The adjusted mean difference in change from baseline in HbA_1c with empagliflozin versus glimepiride was −0.11% (95% CI, −0.19 to −0.02; P = .015 for superiority; see Figure 1). The investigators also observed significant reductions with empagliflozin in body weight (−3.1 vs 1.3 kg; P < .001), systolic blood pressure (−3.1 vs 2.5 mm Hg; P < .001), and diastolic blood pressure (−1.8 vs 0.9 mm Hg; P < .001). The incidence of death was similar in the 2 groups (0.7% vs 0.6%).

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Figure 1.

Change in Mean HbA_1c From Baseline at 104 Weeks

Reprinted from The Lancet Diabetes & Endocrinology, 2, Ridderstrale M et al, Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial, 691–700, Copyright 2014, with permission from Elsevier.

Empagliflozin was also associated with significantly fewer hypoglycemic adverse events (AEs) than glimepiride (24% vs 3%; P < .001). In the empagliflozin group, serious AEs were reported in 16% of patients, compared with 11% in the glimepiride group. The incidence of AEs leading to treatment discontinuation was similar in both groups (5% vs 4%). Urinary tract infection was recorded in 13.7% and 13.1% of patients receiving empagliflozin and glimepiride, respectively, and genital infection in 11.8% and 2.2% of patients, respectively.

Prof Ridderstråle concluded that, compared with glimepiride, empagliflozin as add-on therapy to metformin produced a small but significantly superior difference in the reduction of HbA_1c and provided sustained reductions in body weight and blood pressure. Patients treated with empagliflozin had fewer AEs, particularly hypoglycemia.

• © 2014 MD Conference Express®