Outcome trial with SGLT2 inhibitor met its primary endpoint in T1DM patients
Presented at the European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin, Germany (1-5 October).
Empagliflozin met the primary efficacy endpoint, defined as a change from baseline in HbA1c versus placebo after 26 weeks of treatment, for all doses investigated (2.5, 10 and 25 mg) in the Empagliflozin as Adjunctive to inSulin thErapy (EASE) Phase III program in adults with T1DM.
Empagliflozin is currently not approved for use in T1DM.
The EASE-2 study evaluated doses of 10 and 25 mg of empagliflozin as adjunct to insulin over 52 weeks, while the EASE-3 study evaluated doses of 2.5, 10 and 25 mg of empagliflozin as adjunct to insulin over 26 weeks. In EASE-2, placebo-corrected mean change from baseline in HbA1c at week 26 was -0.54% and -0.53% for empagliflozin 10 and 25 mg, respectively. In EASE-3 placebo-corrected mean change from baseline in HbA1c at week 26 was -0.28%, -0.45% and -0.52% for empagliflozin 2.5 and 10 and 25 mg, respectively. In addition to reduction in HbA1c, empagliflozin treatment was effective on secondary endpoints, showing reductions in weight, decreases in BP, and decreases in total daily insulin dose.
In addition, data from continuous glucose monitoring in the EASE program indicates that patients treated with empagliflozin had improved glycemic variability and spent more time in range, although the data for the 2.5 mg dose are limited.
There was no increase in the risk of investigator-reported hypoglycemic events, including severe hypoglycemia, with empagliflozin treatment, which was a key secondary endpoint in the trials. Additionally, a reduction in patient-reported hypoglycemic events was observed. The number of adjudicated diabetic ketoacidosis (DKA) events was comparable between empagliflozin 2.5 mg and placebo, and higher than placebo with empagliflozin 10 and 25 mg. Apart from incidence of DKA, the safety profile observed in the EASE program was generally consistent with the previously reported safety profile of empagliflozin in adults with T2DM.
The goal of the EASE program was to determine if treatment with empagliflozin could benefit people with T1DM as an adjunct to insulin. Given the risk of DKA for people with T1DM, the 2.5 mg empagliflozin dose warrants consideration, as it balances glycemic and metabolic improvements that are relevant to patients without increasing their risk of DKA or other serious adverse events.
The EASE program demonstrated that empagliflozin helps patients with T1DM to remain within their target glucose range better than insulin alone. There are currently no oral treatment options available for people with T1DM and these results show that empagliflozin could benefit these individuals.
The EASE Phase III program includes two multinational, double-blinded, placebo-controlled Phase III clinical trials to investigate the efficacy, safety and tolerability of once-daily empagliflozin in adults with T1DM, an indication for which empagliflozin is currently not approved.
EASE-2 evaluated 10 and 25 mg doses of empagliflozin as adjunct to insulin versus placebo for 52 weeks in 720 patients. The primary endpoint was change from baseline in HbA1c after 26 weeks of treatment. EASE-3 compared 2.5, 10 and 25 mg doses of empagliflozin as adjunct to insulin versus placebo for 26 weeks in 960 patients. The primary endpoint was change from baseline in HbA1c after 26 weeks of treatment.
- Our reporting is based on the information provided by the EASD press service -