Exploration of the clinical benefits of sodium glucose co-transporter 2 inhibitors in diabetic patients with concomitant heart failure

Abstract

Prevention and treatment strategies for heart failure (HF) in diabetes have not been fully established, at least partly due to lack of recognition of a pathological link between the two and effective antidiabetic agents for HF. Recent cardiovascular (CV) outcomes trials demonstrated that treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors greatly improved major CV adverse events in type 2 diabetes (T2D) patients at high risk for CV events, seemingly driven by risk reduction in HF-related outcomes. The beneficial effects of SGLT2 inhibitors on such outcomes and the heart itself are unique characteristics among antidiabetic agents, and SGLT2 inhibitors are expected to be a promising therapeutic option for CV disease and HF care. However, because a limited number of T2D patients with concomitant HF were included in the CV outcomes trials, the treatment effects of SGLT2 inhibitors for such conditions have not been fully investigated. Moreover, there has been little evidence to suggest SGLT2 inhibitor mediated effects on CV function and relevant biomarkers. Januzzi et al. (J Am Coll Cardiol 70: 704-712, 2017) reported that canagliflozin treatment could delay the escalation of cardiac biomarkers in older T2D patients, suggesting direct CV protection by SGLT2 inhibitors in this population. Whether SGLT2 inhibitors can exert similar benefits in T2D patients with concomitant HF will likely be the next big issue of medical concern. Furthermore, newer clinical trials are currently ongoing to investigate whether SGLT2 inhibitors exhibit beneficial effects for HF, both in the presence and absence of T2D. Such trials may potentially identify novel approaches for treating HF.

Fig. 1

Comparison of the treatment effects of SGLT2 inhibitors on CV death and hospitalization for HF, stratified according to the presence or absence of history of HF at baseline. In the EMPA-REG OUTCOME trial, both outcomes were significantly decreased in the subgroups without HF at baseline, while in the CANVAS Program, the outcomes were reduced in the subgroups with HF at baseline, although there was no statistically significant treatment effect across the subgroups. CV cardiovascular, HF heart failure, SGLT2 sodium glucose co-transporter 2