RT Journal Article
SR Electronic
T1 Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 2560
OP 2569
DO 10.2337/dc18-1749
VO 41
IS 12
A1 Rosenstock, Julio
A1 Marquard, Jan
A1 Laffel, Lori M.
A1 Neubacher, Dietmar
A1 Kaspers, Stefan
A1 Cherney, David Z.
A1 Zinman, Bernard
A1 Skyler, Jay S.
A1 George, Jyothis
A1 Soleymanlou, Nima
A1 Perkins, Bruce A.
YR 2018
UL http://care.diabetesjournals.org/content/41/12/2560.abstract
AB OBJECTIVE To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program (N = 1,707) included two double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg (n = 243), 25 mg (n = 244), and placebo (n = 243), 52-week treatment; and EASE-3 with empagliflozin 2.5 mg (n = 241), 10 mg (n = 248), 25 mg (n = 245), and placebo (n = 241), 26-week treatment. Together they evaluated empagliflozin 10 mg and 25 mg, doses currently approved in treatment of type 2 diabetes, and additionally 2.5 mg on 26-week change in glycated hemoglobin (primary end point) and weight, glucose time-in-range (>70 to ≤180 mg/dL), insulin dose, blood pressure, and hypoglycemia.RESULTS The observed largest mean placebo-subtracted glycated hemoglobin reductions were −0.28% (95% CI −0.42, −0.15) for 2.5 mg, −0.54% (−0.65, −0.42) for 10 mg, and −0.53% (−0.65, −0.42) for 25 mg (all P < 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by −1.8/−3.0/−3.4 kg (all P < 0.0001); increased glucose time-in-range by +1.0/+2.9/+3.1 h/day (P < 0.0001 for 10 and 25 mg); lowered total daily insulin dose by −6.4/−13.3/−12.7% (all P < 0.0001); and decreased systolic blood pressure by −2.1/−3.9/−3.7 mmHg (all P < 0.05). Genital infections occurred more frequently on empagliflozin. Adjudicated diabetic ketoacidosis occurred more with empagliflozin 10 mg (4.3%) and 25 mg (3.3%) but was comparable between empagliflozin 2.5 mg (0.8%) and placebo (1.2%). Severe hypoglycemia was rare and frequency was similar between empagliflozin and placebo.CONCLUSIONS Empagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with 10 mg and 25 mg. Ketone monitoring for early ketoacidosis detection and intervention and lower empagliflozin doses may help to reduce this risk.