Effect of empagliflozin when added to insulin in patients with type 2 diabetes and established cardiovascular disease: Results from the EMPA-REG OUTCOME trial

Aim:

To investigate changes in HbA_1c and weight, hypoglycaemia and cardiovascular outcomes in patients with type 2 diabetes (T2DM) and established cardiovascular disease taking insulin at baseline in EMPA-REG OUTCOME.

Methods:

Patients were randomised to empagliflozin 10 mg or 25 mg or placebo. Background glucose-lowering therapy was to remain unchanged for 12 weeks then be adjusted according to local guidelines.

Results:

Of 2333, 2345 and 2342 patients that received placebo, empagliflozin 10 mg and empagliflozin 25 mg, 48.6%, 48.3% and 47.8%, respectively, were taking insulin at baseline. Mean baseline insulin dose was similar between treatment groups, and decreased with empagliflozin and increased with placebo at study end. Confirmed hypoglycaemic adverse events (plasma glucose ≤70 mg/dL and/or requiring assistance) were reported in 42.6%, 43.6% and 41.4% of patients on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. At week 164, adjusted mean (95% CI) differences vs. placebo in change from baseline in HbA_1c (%) were -0.24 (-0.37, -0.11) and -0.35 (-0.48, -0.22) with empagliflozin 10 mg and 25 mg, respectively, and in weight (kg) were -1.9 (-2.5, -1.4) and

-2.2 (-2.7, -1.6), respectively. Risk reductions with empagliflozin vs. placebo in cardiovascular death, hospitalisation for heart failure and all-cause mortality were similar in patients taking and not taking insulin.

Conclusion:

In patients with T2DM and established cardiovascular disease receiving insulin at baseline, empagliflozin reduced HbA_1c and weight, without increased hypoglycaemia, vs. placebo. Risk reductions in cardiovascular outcomes and all-cause mortality with empagliflozin in this subgroup were consistent with the overall population.