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 P P P P 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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Use of preventative processes may have contributed to the lower rates of ketoacidosis seen in some studies of SGLT inhibitors for adjunctive glycemic management in type 1 diabetes compared with those that did not include preventative strategies.
“Use of these processes may have contributed to the lower rates of ketoacidosis seen in some of the studies of these agents for adjunctive glycemic management in people with type 1 diabetes (314-316) compared with those that did not include preventative strategies (310,317).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [314]
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- Authors
- Rosenstock, J., Marquard, J., Laffel, L. M., Neubacher, D., Kaspers, S., Cherney, D. Z., Zinman, B., Skyler, J. S., George, J., Soleymanlou, N., & Perkins, B. A.
- Affiliations
- Dallas Diabetes Research Center (US)
- Boehringer Ingelheim (Germany) (DE)
- Joslin Diabetes Center (US)
- University of Toronto (CA)
- Mount Sinai Hospital (CA)
- University of Miami (US)
- Boehringer Ingelheim (Canada) (CA)
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2018-10-04
- Volume
- 41
- Issue
- 12
- Pages
- 2560-2569
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2894624538
- Cited by
- 363
- References
- 9
- Citations by year
- 2026: 32 · 2025: 54 · 2024: 39 · 2023: 49 · 2022: 31 · 2021: 45 · 2020: 55 · 2019: 52 · 2018: 6
- FWCI
- 31.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boehringer Ingelheim
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- empagliflozin, type 1 diabetes, adjunctive therapy, intensive insulin therapy, HbA1c, weight loss, insulin dose reduction, hypoglycemia, SGLT2 inhibitors, dose comparison, blood pressure, treatment efficacy and safety, glycemic control, hypoglycemia risk
- MeSH terms
- Adult, Aged, Benzhydryl Compounds, Blood Glucose, Diabetes Mellitus, Type 1, Double-Blind Method, Drug Therapy, Combination, Female, Glucosides, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Placebos, Weight Loss, Treatment Outcome
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