Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials
- PMID: 30287422
- DOI: 10.2337/dc18-1749
Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials
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 -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.
Trial registration: ClinicalTrials.gov NCT02414958 NCT02580591.
© 2018 by the American Diabetes Association.
Comment in
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SGLT Inhibitors for Type 1 Diabetes: An Obvious Choice or Too Good to Be True?Diabetes Care. 2018 Dec;41(12):2444-2447. doi: 10.2337/dci18-0041. Diabetes Care. 2018. PMID: 30459245 No abstract available.
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Empagliflozin as an adjunctive therapy for type 1 diabetes.Ann Transl Med. 2018 Dec;6(Suppl 2):S134. doi: 10.21037/atm.2018.12.52. Ann Transl Med. 2018. PMID: 30740455 Free PMC article. No abstract available.
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