Type 2 diabetes mellitus (T2DM) is known to be associated with a 33% greater risk of hospitalization for heart failure (HF) and an increase in the risk of cardiovascular and overall death.¹ Patients with coexisting T2DM and chronic kidney disease (CKD) are at further risk of HF and ischemic events that can lead to cardiovascular death.^2,3 Previously, several sodium-glucose cotransporter 2 inhibitors (SGLT2is) were demonstrated to lower the risk of cardiovascular death or hospitalization for HF, particularly in HF patients with reduced ejection fraction (HFrEF).^4,5 Recently, the SGLT2i sotagliflozin, which also has SGLT1 inhibition capacity, has demonstrated a significant reduction in the risk of death from cardiovascular causes, HF hospitalizations and urgent HF visits when being used soon after an episode of decompensated HF regardless of the presence of albuminuria in patients with CKD.^2,6

Sotagliflozin is a unique SGLT2i which has shown an inhibitory effect on the gastrointestinal SGLT1.² While there is increasing evidence demonstrating the effectiveness of SGLT2i among patients with HFrEF, the safety and efficacy of initiating SGLT2i soon after an episode of decompensated HF remain unknown.^4-6 Also, while there are positive results from randomized trials supporting the use of SGLT2i in CKD patients with or without diabetes, all these trials required patients to have macroalbuminuria and reduced estimated glomerular filtration rate (eGFR) to be included.² As a result, further investigation would also be required to confirm the safety and efficacy of SGLT2i in CKD patients with or without albuminuria.² Two new trials, SCORED and SOLOIST-WHF, have recently added more data to support the use of sotagliflozin.

Firstly, the SOLOIST-WHF trial aimed to evaluate the efficacy of sotagliflozin in reducing cardiovascular risks among T2DM patients who had recent worsening HF, with or without HFrEF.⁶ In this phase 3, double-blind, randomized, placebo-controlled trial, the initiation of sotagliflozin soon after an episode of worsening HF significantly lowered the rate of death from cardiovascular causes, HF hospitalizations and urgent HF visits when compared to placebo (51.0 vs. 76.3 events per 100 patients-years; HR=0.67; 95% CI: 0.52-0.85; p<0.001).⁶ Consistent efficacy was also observed across prespecified subgroups including patients who received sotagliflozin or placebo before or after hospital discharge, regardless of the left ventricular ejection fraction.⁶

On the other hand, the SCORED trial, a multicenter, phase 3, doubleblind, randomized, placebo-controlled trial, was conducted to evaluate the efficacy of sotagliflozin in preventing cardiovascular events among T2DM patients with CKD, with or without albuminuria.² Regardless of the presence of albuminuria, sotagliflozin also significantly lowered the rate of death from cardiovascular causes, HF hospitalizations and urgent HF visits when compared to placebo (5.6 vs. 7.5 events per 100 patientsyears; HR=0.74; 95% CI: 0.63-0.88; p<0.001).² In addition, sotagliflozin significantly delayed the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (HR=0.84; 95% CI: 0.72-0.99), and the first occurrence of death from cardiovascular causes or hospitalization for HF (HR=0.77; 95% CI: 0.66-0.91).²