Emerging sodium-glucose cotransporter-2 inhibitor therapies for managing heart failure in patients with chronic kidney disease

ABSTRACT

Introduction

Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have risen in popularity for managing heart failure (HF) and chronic kidney disease (CKD), little guidance is available for the management of patients with an overlap of HF and CKD.

Areas covered

Following a brief review of the cardiorenal effects of SGLT2 inhibitors, this narrative review focused on the published clinical evidence pertaining to the cardiovascular and renal efficacy of SGLT2 inhibitors in patients with HF and CKD, including both randomized controlled trials and real-world observational studies. Real-world considerations of using SGLT2 inhibitors in these patients were also reviewed.

Expert opinion

Although no randomized controlled trial has specifically studied the use of SGLT2 inhibitors in patients with HF and CKD, evidence from existing trials is largely sufficient to demonstrate that SGLT2 inhibitors are efficacious in these patients, in whom these agents should be initiated early to maximally slow declines in renal function. Further studies should focus on better guiding the timing of initiating SGLT2 inhibitors, improving these agents’ cost-effectiveness, and bettering equity of access to these agents. Further areas of study may include the prognostic implications of SGLT2 inhibitors-induced changes in biomarker levels (e.g. natriuretic peptides), and the potentials of SGLT1 inhibition.

KEYWORDS:

• SGLT-2
• heart failure
• chronic kidney disease
• cardiorenal
• pharmacotherapy

Article highlights

• Although no RCT to date was specifically powered to study the efficacy of SGLT2 inhibitors for treating patients with HF and CKD, evidence from multiple-existing RCTs has sufficiently demonstrated the efficacy of SGLT2 inhibitors in these patients.

• As RCTs are known to have limited real-world generalizability, observational studies remain required to evaluate whether the efficacy reported in RCTs is translatable to real-life practice, especially since patients with both HF and CKD often have multiple comorbidities and are medically complex.

• Given the striking benefits of SGLT2 inhibitors, their capability in slowing declines in renal function, and that they are contraindicated in severe renal impairment, SGLT2 inhibitors should be started as early as pragmatically possible in patients with HF and CKD to maximally slow declines in renal function. However, these patients are often medically complex and necessitate careful consideration of multiple factors when using SGLT2 inhibitors.

• Further research and implementation efforts should focus on better guiding the initiation of SGLT2 inhibitors in patients with HF and CKD, especially during hospitalization, improving the cost-effectiveness of these agents, and bettering equity in accessing these agents.

• Further studies may also consider exploring the prognostic implications of SGLT2 inhibitor-induced changes in natriuretic peptides in patients with HF and CKD, as well as the potential value of SGLT1 inhibition alone or in combination with SGLT2 inhibition.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Abbreviations

CKD	=	chronic kidney disease
DM	=	diabetes mellitus
eGFR	=	estimated glomerular filtration rate
HF	=	heart failure
HFmrEF	=	heart failure with mildly reduced ejection fraction
HFpEF	=	heart failure with preserved ejection fraction
HFrEF	=	heart failure with reduced ejection fraction
HR	=	hazard ratio
KDIGO	=	Kidney Disease: Improving Global Outcomes
RCT	=	randomized controlled trial
SGLT1	=	sodium-glucose cotransporter-1
SGLT2	=	sodium-glucose cotransporter-2

Additional information

Funding

This paper was not funded.