Positive Results for Empagliflozin in Type 1 Diabetes Trials
Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor.
Results from the Phase 3 EASE program showed that treatment with empagliflozin, as an adjunct to insulin in patients with type 1 diabetes, led to improved glycemic control without increasing hypoglycemia. Findings were presented at the EASD Annual Congress and published online in the journal Diabetes Care.
Empagliflozin (Jardiance; Boehringer Ingelheim and Lilly), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is currently approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) and to reduce the risk of cardiovascular (CV) death in adults with T2D and established CV disease.
The EASE Phase 3 program included 2 double-blind, placebo-controlled trials investigating the efficacy and safety of empagliflozin as an adjunct to insulin therapy in adults with type 1 diabetes. In EASE-2 (N=720), empagliflozin 10mg and 25mg doses were evaluated vs placebo, while in EASE-3 (N=960), 2.5mg, 10mg, and 25mg doses of empagliflozin were compared with placebo.
Results from EASE-2 showed that the placebo-corrected mean change from baseline in HbA1C for the 10mg and 25mg doses was -0.54% and -0.53%, respectively, at week 26. EASE-3 results showed that the placebo-corrected mean change from baseline in HbA1C at week 26 was ‑0.28%, -0.45% and -0.52% for empagliflozin 2.5mg, 10mg and 25mg, respectively. In addition, treatment with empagliflozin was associated with reduced mean weight, increased glucose time-in-range, reduced total daily insulin dose, and decreased systolic blood pressure.
With regard to safety, severe hypoglycemia was found to be rare and the frequency was similar between empagliflozin and placebo. Moreover, while the number of adjudicated diabetic ketoacidosis (DKA) events was higher with empagliflozin 10mg (4.3%) and 25mg (3.3%), DKA incidence was comparable between empagliflozin 2.5mg (0.8%) and placebo (1.2%).
"Given the risk of diabetic ketoacidosis for people with type 1 diabetes, the 2.5mg 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," said Bernard Zinman, MD, professor in the Department of Medicine, University of Toronto and scientist at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
In a press release, Boehringer Ingelheim stated that they have initiated regulatory discussions based on the results of the EASE program. "Given that less than one third of adults with type 1 diabetes in the US consistently meet target blood sugar levels solely with insulin, we look forward to working with the US Food and Drug Administration to explore whether this potential treatment can be made available to people with type 1 diabetes," said Thomas Seck, MD, senior vice president, Medicine and Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.
For more information visit care.diabetesjournals.org.