Abstract
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 20.28% (95% CI 20.42, 20.15) for 2.5 mg, 20.54% (20.65, 20.42) for 10 mg, and 20.53% (20.65, 20.42) for 25 mg (all P < 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by 21.8/23.0/23.4 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 26.4/213.3/212.7% (all P < 0.0001); and decreased systolic blood pressure by 22.1/23.9/23.7 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2560-2569 |
| Number of pages | 10 |
| Journal | Diabetes Care |
| Volume | 41 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Advanced and Specialized Nursing
Cite this
Empagliflozin as adjunctive to insulin therapyin type 1 diabetes : The EASE trials. / Rosenstock, Julio; Marquard, Jan; Laffel, Lori M.; Neubacher, Dietmar; Kaspers, Stefan; Cherney, David Z.; Zinman, Bernard; Skyler, Jay S; George, Jyothis; Soleymanlou, Nima; Perkins, Bruce A.
In: Diabetes Care, Vol. 41, No. 12, 01.12.2018, p. 2560-2569.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Empagliflozin as adjunctive to insulin therapyin type 1 diabetes
T2 - The EASE trials
AU - Rosenstock, Julio
AU - Marquard, Jan
AU - Laffel, Lori M.
AU - Neubacher, Dietmar
AU - Kaspers, Stefan
AU - Cherney, David Z.
AU - Zinman, Bernard
AU - Skyler, Jay S
AU - George, Jyothis
AU - Soleymanlou, Nima
AU - Perkins, Bruce A.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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 20.28% (95% CI 20.42, 20.15) for 2.5 mg, 20.54% (20.65, 20.42) for 10 mg, and 20.53% (20.65, 20.42) for 25 mg (all P < 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by 21.8/23.0/23.4 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 26.4/213.3/212.7% (all P < 0.0001); and decreased systolic blood pressure by 22.1/23.9/23.7 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.
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 20.28% (95% CI 20.42, 20.15) for 2.5 mg, 20.54% (20.65, 20.42) for 10 mg, and 20.53% (20.65, 20.42) for 25 mg (all P < 0.0001). Empagliflozin 2.5/10/25 mg doses, respectively, reduced mean weight by 21.8/23.0/23.4 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 26.4/213.3/212.7% (all P < 0.0001); and decreased systolic blood pressure by 22.1/23.9/23.7 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.
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U2 - 10.2337/dc18-1749
DO - 10.2337/dc18-1749
M3 - Article
VL - 41
SP - 2560
EP - 2569
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 12
ER -