Low‐dose empagliflozin as adjunct‐to‐insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy
| العنوان: | Low‐dose empagliflozin as adjunct‐to‐insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy |
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| المؤلفون: | Matthew M. Riggs, Julio Rosenstock, Lori M. Laffel, Rena J. Eudy-Byrne, Ahmed Elmokadem, Jan Marquard, Bruce A. Perkins, Nima Soleymanlou, Valerie Nock, Dietmar Neubacher, Curtis K. Johnston, Karl Heinz Liesenfeld, Jay S. Skyler, Jyothis T. George |
| المصدر: | Diabetes, Obesity & Metabolism |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.medical_specialty, Diabetic ketoacidosis, type 1 diabetes, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, empagliflozin, Urology, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, sodium‐glucose co‐transporter‐2 inhibitor, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Glucosides, Pharmacokinetics, Internal Medicine, Empagliflozin, medicine, Humans, Hypoglycemic Agents, Insulin, Benzhydryl Compounds, education, Glycated Hemoglobin, antidiabetic drug, education.field_of_study, Type 1 diabetes, Dose-Response Relationship, Drug, business.industry, Low dose, Original Articles, medicine.disease, Dose–response relationship, Diabetes Mellitus, Type 1, dose–response relationship, Drug Therapy, Combination, Original Article, business |
| الوصف: | Aim To confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE‐3 by modelling and simulation analyses. Materials and methods Independent of data from EASE‐3 that tested 2.5 mg, we simulated the effect of a 2.5 mg dose through patient‐level, exposure‐response modelling in the EASE‐2 clinical study. A primary semi‐mechanistic model evaluated efficacy considering clinical insulin dose adjustments made after treatment initiation that potentially limited HbA1c reductions. The model was informed by pharmacokinetic, insulin dose, mean daily glucose and HbA1c data, and was verified by comparing the simulations with the observed HbA1c change in EASE‐3. One of two empagliflozin phase 3 trials in type 1 diabetes (EASE‐3 but not EASE‐2) included a lower 2.5 mg dose. A placebo‐corrected HbA1c reduction of 0.28% was demonstrated without the increased risk of diabetic ketoacidosis observed at higher doses (10 mg and 25 mg). Since only one trial included the lower dose, we aimed to confirm the observed reduction in HbA1c for the 2.5 mg dose by modelling and simulation analyses. Results The simulated 26‐week mean HbA1c change was −0.41% without insulin dose adjustment and −0.29% at 26 weeks with insulin dose adjustment. A simplified (descriptive) model excluding insulin dose and mean daily glucose confirmed the –0.29% HbA1c change that would have been observed had the EASE‐2 population received a 2.5 mg dose for 26/52 weeks. Conclusions The HbA1c benefit of low‐dose empagliflozin directly observed in the EASE‐3 trial was confirmed by two modelling and simulation approaches. |
| تدمد: | 1463-1326 1462-8902 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00156de9e54d639a6362625fbc0b0cf0Test https://doi.org/10.1111/dom.13945Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....00156de9e54d639a6362625fbc0b0cf0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14631326 14628902 |
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