Reviwer : Dr. Süleyman Çağan Efe

Name of the Study : Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure - SOLOIST-WHF

Published in Congress : ACC 2021

Link : https://www.nejm.org/doi/full/10.1056/NEJMoa2030183

Background  :

The prior DAPA-HF study , dapagliflozin heart failure patients and in the EMPEROR-Reduced study empagliflozin in HF patients with reduced EF , demonstrated the mortality and morbidity benefits of SGLT2 inhibitors independent of T2DM status. The results of the EMPEROR-preserved trial are expected to be announced at ESC 2021. Sotagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, but also acts by inhibiting SGLT1, which is found primarily in the gut and appears to delay glucose absorption.

Objective  :

The aim of this study was to evaluate the safety and efficacy of sotagliflozin in reducing cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM) and recent heart failure.

Method :

Patients who admitted to hospital due to heart failure,  with T2DM, hemodynamically stable condition and taking oral diuretic therapy, measured B-type natriuretic peptide (BNP) levels ?150 pg/ml (if atrial fibrillation ?450 pg/ml) or N-terminal pro-BNP levels ?  600 pg/ml (?1800 pg/ml if atrial fibrillation) were included in the study . Patients were randomized 1:1 to receive sotagliflozin 400 mg daily (n = 608) or placebo (n = 614). Sotagliflozin patients were started on 200 mg daily and increased to the target dose if there were no side effects. The drug was started in patients before or within 3 days of discharge. Patients with end-stage heart failure, patients who had recently undergone percutaneous or surgical revascularization, and patients with a glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 were excluded. The mean follow-up period was 9 months, the mean patient age was 69 years, the percentage of female patients was 34%, the use of RAAS was 92%, and the use of metformin was 52%.

Results :

Although the study was terminated prematurely due to COVID-19 . Taking total CV death, HF hospitalization, or emergency visit for HF as the primary endpoint, 70/100 - 98/100 event patient-years were observed for sotagliflozin vs. placebo (hazard ratio 0.67, 95% [CI] 0.52-0.85, p = 0.0009). This result became significant at 28 days of follow-up. Looking at secondary outcomes for sotagliflozin versus placebo, total cardiovascular death from HF and hospitalization for heart failure: 60/100 vs. 86/100 event patient-years (p = 0.003), First CV death and heart failure hospitalization was  33% versus 48% (p = 0.003) The change in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score was significantly different between the groups: 17.7 versus 13.6 (p = 0.005) . However, cardiovascular death: 10.6/100 vs. 12.5/100 patient-years (p = 0.36) and change in eGFR: -0.34 vs -0.18 (p = 0.78) were similar between groups. Although diarrhea as a side effect was significantly different between the groups, genital infection and severe hypoglycemia were similar between the groups.

Conclusion :

The SOLOIST-WHF study demonstrated that sotagliflozin has positive effects on CV outcomes in patients with T2DM and heart failure.

Interpretations :

SOLOIST-WHF is the first large randomized controlled trial to demonstrate that it is safe and effective to initiate SGLT2 inhibition before or shortly after discharge in acute HF in stabilized patients.