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

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 m 2 ); 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.

The functioning in chronic illness –— a key determinant of treatment efficacy in patients with metabolic syndrome

“…Metabolic syndrome (MetS) including obesity, hypertension, impaired glucose metabolism, and elevated non-high-density lipoprotein cholesterol level due to increasing prevalence and serious impact on clinical outcomes constitutes a significant health and social problem [1]. Recently several papers published in "Medical Research Journal" presented different therapeutic approaches in this subset of patients [2][3][4][5][6].…”

Therapeutic strategies targeting metabolic syndrome

“…A review of the PubMed database showed that the number of publications on MetS is growing rapidly, reaching over 106,000 publications this year. In the current issue of the Medical Research Journal, as many as four publications concern various treatment strategies for patients with obesity and metabolic syndrome [2][3][4][5]. The first one is the rationale and protocol of the DEMETER -SIRIO 11 study that is aimed at comparative evaluation of the effect of two doses of empagliflozin (10 mg vs. 20 mg) on reduction of BMI and HbA1c in patients with MetS.…”

“…The first one is the rationale and protocol of the DEMETER -SIRIO 11 study that is aimed at comparative evaluation of the effect of two doses of empagliflozin (10 mg vs. 20 mg) on reduction of BMI and HbA1c in patients with MetS. The study is designed as a phase III, multicenter, randomized, open-label, investigator-initiated clinical trial with a 6-month follow-up [2]. The second publication is a report of study results aimed to determine whether the volume of the resected part of the stomach correlates with postoperative results after 1-year follow-up.…”