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Vol 8, No 3 (2023)
Original article
Published online: 2023-09-08
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Efficacy of double vs. standard empagliflozin dose for METabolic syndromE tReatment (DEMETER — SIRIO 11) study. Rationale and protocol of the study

Jacek Kubica1, Aldona Kubica2, Zofia Grąbczewska1, Paweł Stróżecki3, Piotr Adamski1, Andrzej Brymora3, Rafał Donderski3, Tomasz Fabiszak1, Mariusz Flisiński3, Robert Gajda4, Beata Januszko-Giergielewicz5, Przemysław Magielski6, Piotr Michalski2, Michał Kasprzak1, Agata Kosobucka-Ozdoba2, Ewa Laskowska1, Gavino Casu7, Eliano Pio Navarese7, Piotr Niezgoda1, Małgorzata Ostrowska1, Łukasz Pietrzykowski2, Grzegorz Skonieczny8, Beata Sulikowska3, Łukasz Szarpak910, Paweł Szymański11, Julia Maria Umińska12, Paweł Zalewski1314
DOI: 10.5603/mrj.97187
·
Medical Research Journal 2023;8(3):171-178.
Affiliations
  1. Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
  2. Department of Cardiac Rehabilitation and Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
  3. Department of Nephrology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
  4. Gajda-Med Medical Center in Pułtusk, Pułtusk, Poland.
  5. Department of General, Liver and Transplant Surgery, Collegium Medicum, Nicolaus Copernicus University
  6. Scientia Research Institute Sp. z o.o., Bydgoszcz, Poland
  7. Department of Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy
  8. Chair of the Cardiology Clinic Ward and Acute Cardiac Care Unit, Wojewodzki Szpital Zespolony im. L. Rydygiera, Torun, Poland, Poland
  9. Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine Houston, Houston, TX, USA, United States
  10. Institute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, Warsaw, Poland, Poland
  11. Department of Cardiology, Interventional Cardiology and Electrophysiology with Cardiac Intensive Care Unit, Tertiary Care Hospital in Grudziadz, Poland
  12. Department of Geriatrics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
  13. Department of Exercise Physiology and Functional Anatomy, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
  14. Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Warsaw Medical University, Warsaw, Poland

open access

Vol 8, No 3 (2023)
ORIGINAL ARTICLES
Published online: 2023-09-08

Abstract

Complex metabolic disorders associated with obesity and diabetes pose a serious therapeutic challenge. The DEMETER-SIRIO 11 study is a phase III, multicenter, randomized, open-label, investigator-initiated clinical trial with a 6-month follow-up aimed at performing a comparative evaluation of the effect of two empagliflozin doses (10 mg vs. 20 mg) on selected metabolic parameters in patients with metabolic syndrome. The primary hypothesis of the study is that a higher dose of empagliflozin will result in a significant reduction of BMI and HbA1c in patients with obesity and MS receiving empagliflozin 20 mg as compared to 10 mg. Sample size and power calculation were based on a superiority assumption for the primary efficacy endpoint (the difference in decrease of body weight by > 1.5 kg and HbA1c by > 0.4%) for the higher vs. standard dose arm at 6-months of follow-up. Therefore, a sample size of 79 patients per arm is required to provide 80% power to detect a higher decrease in BMI, and 85 patients per arm is required to provide 80% power to detect a higher decrease in HbA1c in the 20 mg versus 10 mg arm with a type I error rate of 0.05. Summing up, enrollment of a total of 200 patients (100 in each arm) is planned to compensate for the potential drop-out rate from the study of up to 15%. Prespecified subanalyses will be performed according to: 1) diabetes mellitus; 2) chronic kidney disease (GFR < 60 mL/min/1.73 m2); 3) gender; and 4) age.

A greater comprehensive improvement in biochemical, functional, and anthropometric parameters reflecting favorable metabolic changes is expected at the higher dose of empagliflozin compared to the standard dose.

Abstract

Complex metabolic disorders associated with obesity and diabetes pose a serious therapeutic challenge. The DEMETER-SIRIO 11 study is a phase III, multicenter, randomized, open-label, investigator-initiated clinical trial with a 6-month follow-up aimed at performing a comparative evaluation of the effect of two empagliflozin doses (10 mg vs. 20 mg) on selected metabolic parameters in patients with metabolic syndrome. The primary hypothesis of the study is that a higher dose of empagliflozin will result in a significant reduction of BMI and HbA1c in patients with obesity and MS receiving empagliflozin 20 mg as compared to 10 mg. Sample size and power calculation were based on a superiority assumption for the primary efficacy endpoint (the difference in decrease of body weight by > 1.5 kg and HbA1c by > 0.4%) for the higher vs. standard dose arm at 6-months of follow-up. Therefore, a sample size of 79 patients per arm is required to provide 80% power to detect a higher decrease in BMI, and 85 patients per arm is required to provide 80% power to detect a higher decrease in HbA1c in the 20 mg versus 10 mg arm with a type I error rate of 0.05. Summing up, enrollment of a total of 200 patients (100 in each arm) is planned to compensate for the potential drop-out rate from the study of up to 15%. Prespecified subanalyses will be performed according to: 1) diabetes mellitus; 2) chronic kidney disease (GFR < 60 mL/min/1.73 m2); 3) gender; and 4) age.

A greater comprehensive improvement in biochemical, functional, and anthropometric parameters reflecting favorable metabolic changes is expected at the higher dose of empagliflozin compared to the standard dose.

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Keywords

empagliflozin, metabolic syndrome, obesity, randomized clinical study

About this article
Title

Efficacy of double vs. standard empagliflozin dose for METabolic syndromE tReatment (DEMETER — SIRIO 11) study. Rationale and protocol of the study

Journal

Medical Research Journal

Issue

Vol 8, No 3 (2023)

Article type

Original article

Pages

171-178

Published online

2023-09-08

Page views

301

Article views/downloads

383

DOI

10.5603/mrj.97187

Bibliographic record

Medical Research Journal 2023;8(3):171-178.

Keywords

empagliflozin
metabolic syndrome
obesity
randomized clinical study

Authors

Jacek Kubica
Aldona Kubica
Zofia Grąbczewska
Paweł Stróżecki
Piotr Adamski
Andrzej Brymora
Rafał Donderski
Tomasz Fabiszak
Mariusz Flisiński
Robert Gajda
Beata Januszko-Giergielewicz
Przemysław Magielski
Piotr Michalski
Michał Kasprzak
Agata Kosobucka-Ozdoba
Ewa Laskowska
Gavino Casu
Eliano Pio Navarese
Piotr Niezgoda
Małgorzata Ostrowska
Łukasz Pietrzykowski
Grzegorz Skonieczny
Beata Sulikowska
Łukasz Szarpak
Paweł Szymański
Julia Maria Umińska
Paweł Zalewski

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