Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug‑naive patients with type 2 diabetes: a double‑blind extension of a Phase III randomized controlled trial

Roden M, Merker L, Christiansen AV, et al.
Cardiovasc Diabetol (2015) 14:154

Background

In patients with type 2 diabetes mellitus (T2DM), inhibition of the sodium glucose cotransporter 2 (SGLT2) leads to increased urinary glucose excretion (UGE) and reduction in plasma glucose levels, at low risk of hypoglycaemia [1–4]. Empagliflozin is a selective SGLT2 inhibitor that leads to reduction of HbA1c, weight and systolic blood pressure (SBP) compared with placebo [5-7].
In the EMPA-REG MONO™ phase III study, therapy-naïve T2DM patients received either empagliflozin 10 mg, or empagliflozin 25 mg, or sitagliptin 100 mg (a dipeptidyl peptidase-4 inhibitor), or placebo, once daily for 24 weeks. The active study drugs were well tolerated and improved glycaemic control, whereas treatment with empagliflozin also significantly reduced body weight and systolic blood pressure compared with placebo and sitagliptin [6].
This article reports the results of a 52-week extension of the EMPA-REG MONO™ study, with the objective to assess the long-term safety, tolerability and efficacy of empagliflozin 10 mg and 25 mg compared with placebo and sitagliptin as monotherapy in patients with T2DM.

Main results

Efficacy
• HbA1c reductions at week 76 were greater with both doses of empagliflozin compared with placebo. Differences of adjusted means versus placebo were

• empagliflozin 10 mg: −0.78 % (95%CI: −0.94 to −0.63); P < 0.001
• empagliflozin 25 mg: −0.89 % (95%CI: −1.04 to −0.73); P < 0.001

• Adjusted mean changes in HbA1c from baseline to week 76 were greater for empagliflozin 25 mg compared with sitagliptin (differences of adjusted means −0.22 %, 95%CI :−0.38 to −0.07; P = 0.005), but not for empagliflozin 10 mg
• Adjusted mean changes in body weight from baseline to week 76 were

• empagliflozin 10 mg: −1.8 kg (95%CI: −2.4 to −1.3); P < 0.001
• empagliflozin 25 mg: -2.0 kg (95%CI: -2.6 to -1.5); P < 0.001

compared with placebo
• Empagliflozin led to reductions in systolic blood pressure in the primary analysis compared with placebo but not in sensitivity analyses

Safety and tolerability
• Adverse events were reported in 76.8 % of patients on empagliflozin 10 mg, 78.0 % of patients on empagliflozin 25 mg, 76.4 % of patients on placebo and 72.2 % of patients on sitagliptin
• Confirmed hypoglycaemic adverse events (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group
• Adverse events leading to discontinuation were reported in 4.9 % of patients on empagliflozin 10 mg, 4.0 % of patients on empagliflozin 25 mg, 6.6 % of patients on placebo and 4.9 % of patients on sitagliptin.

Conclusion

These data support the hypothesis that in patients with type 2 diabetes mellitus, empagliflozin monotherapy for 76 weeks leads to sustained glycaemic control and reduction in body weight.

Find this article at Cardiovasc Diabetol

References

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