Improving heart failure outcomes with sodium-glucose cotransporter 2 inhibitors in different patient groups

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) were originally developed for the treatment of hyperglycaemia in type 2 diabetes. Because of regulatory requirements to show the safety of this new class of drugs, a large randomized cardiovascular (CV) outcomes trial was completed but this showed that instead of having a neutral effect on heart failure (HF) outcomes, that these drugs could reduce HF outcomes in this population. Subsequent trials with SGLT-2is have shown that HF hospitalizations are reduced by 30% and CV death or HF hospitalization by 21% in patients with type 2 diabetes. These findings have extended to patients with HF with reduced and mildly reduced or preserved ejection fraction in whom further HF hospitalizations are reduced by 28% and CV death or HF hospitalizations reduced by 23%, and that it is becoming a central therapy for the treatment of HF. Moreover, the benefit in patients with HF is observed regardless of the presence or absence of type 2 diabetes. Similarly, in patients with chronic kidney disease and albuminuria, with and without type 2 diabetes, the benefit of SGLT-2is is clearly seen with a 44% reduction in HF hospitalization and 25% reduction in CV death or HF hospitalization. These trials support the use of SGLT-2is in improving HF outcomes in a broad range of patients, from those with type 2 diabetes, chronic kidney disease and those with pre-existing HF regardless of ejection fraction.

Keywords: SGLT-2 inhibitor; cardiovascular disease; drug development; drug mechanism; heart failure.

FIGURE 1

Large prospective randomized trials of sodium‐glucose cotransporter 2 inhibitors in patients with heart failure, type 2 DM and CKD according to the major enrolment criteria. CKD, chronic kidney disease; DM, diabetes mellitus.

FIGURE 2

Rate of heart failure hospitalization in trials of sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes or CKD. CKD, chronic kidney disease.

FIGURE 3

Estimate of treatment effect of sodium‐glucose cotransporter 2 inhibitors (SGLT‐2is) versus placebo on cardiovascular (CV) death or heart failure (HF) hospitalization or HF hospitalization from published meta‐analyses of trials according to major enrolment populations. Estimates for type 2 diabetes (T2DM) taken from Bhatia et al. for heart failure from Vaduganathan et al. for chronic kidney disease (CKD) from Qui et al. and for T2DM and HF and CKD from Baigent et al. HR, hazard ratio.

FIGURE 4

Rate of heart failure (HF) hospitalization in trials of sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes, chronic kidney disease (CKD) or HF. CV, cardiovascular.