medwireNews: The addition of empagliflozin to insulin therapy reduces glycated hemoglobin (HbA1c) levels in patients with type 1 diabetes, indicate findings from the phase III EASE-2 and 3 trials.
Moreover, the results suggest that the use of a 2.5 mg dose of the sodium-glucose cotransporter (SGLT)2 inhibitor – a lower dose than those currently approved for type 2 diabetes – may have a favorable benefit–risk profile in patients with type 1 disease, said the EASE (Empagliflozin as Adjunctive to Insulin Therapy) investigators at the 54th EASD Annual Meeting in Berlin, Germany.
Presenting the efficacy results from EASE-2, Julio Rosenstock (Dallas Diabetes Research Center at Medical City, Texas, USA) reported that the 243 patients who were randomly assigned to receive once daily oral empagliflozin 10 mg and the 241 patients who were allocated to the 25 mg dose experienced significantly greater reductions in average HbA1c levels from baseline to week 26 than the 239 patients in the placebo group.
Specifically, adjusted mean HbA1c levels decreased by 0.54% in the 10 mg group and by 0.53% in the 25 mg group relative to placebo, indicating that “empagliflozin clearly is effective at reducing HbA1c in people with type 1 diabetes,” said Rosenstock.
And in the EASE-3 trial, which included the 2.5 mg daily dose of empagliflozin in addition to those tested in EASE-2, all three doses resulted in a significant improvement in glycemic control compared with placebo, but the magnitude of the reduction in average HbA1c levels relative to placebo (n=238) was smaller for the 237 patients receiving empagliflozin 2.5 mg compared with those given the 10 mg (n=244) and 25 mg (n=242) doses, at 0.28%, 0.45%, and 0.52%, respectively.
Rosenstock described a similar pattern of results for decrease in bodyweight, insulin dose, and systolic blood pressure, with the 2.5 mg dose giving rise to significant reductions relative to placebo, but with the two higher doses having a greater benefit.
Bruce Perkins (University of Toronto, Ontario, Canada), who presented the safety results, said that “so far, the general safety [of empagliflozin in type 1 diabetes] is essentially similar to the known safety profile in type 2 diabetes.”
He reported that the incidence of adverse events (AEs) and serious AEs was “balanced between treatment groups” overall, with corresponding rates of 80.5–89.8% and 5.4–13.0%. There was a greater incidence of genital tract infections among patients treated with empagliflozin versus placebo, but rates were lower among those treated with the 2.5 mg dose compared with the higher doses (5.4 vs 12.8–14.3%).
Rates of investigator-reported hypoglycemia and severe hypoglycemia were not significantly different across the treatment groups, but the incidence of patient-reported hypoglycemia was significantly lower among participants given empagliflozin 10 mg and 25 mg compared with placebo.
Perkins said that, in accordance with previously reported trials of other SGLT2 inhibitors, patients given the two higher doses of empagliflozin had an elevated risk for diabetic ketoacidosis (DKA) compared with placebo-treated patients, with adjudicated rates of 3.3–4.3% versus 1.2%. He stressed, however, that the confirmed rate of DKA was “low and similar to placebo” among participants given the 2.5 mg dose, at 0.8%, suggesting that “lower SGLT2 doses conceivably may help to minimize this risk in [type 1 diabetes].”
Commenting on these findings, Thomas Pieber (Medical University of Graz, Austria) recommended that full dose-response studies, including an additional empagliflozin dose of 5 mg, are “urgently needed” before empagliflozin can be recommended as an adjunct to insulin in type 1 diabetes, and called for biomarker investigations to identify patients at high risk for DKA.
The EASE results have also been published in Diabetes Care.
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