SGLT2 Inhibitors and Cardiovascular Outcomes in Heart Failure

Sodium–glucose cotransporter 2 (SGLT2) inhibitors, originally developed for glycaemic control in diabetes, have emerged as pivotal agents in the management of heart failure. By promoting renal glucose excretion and modest natriuresis, these agents reduce plasma volume and attenuate cardiac preload. Large-scale trials have demonstrated consistent reductions in cardiovascular mortality, hospital admissions for heart failure and progression of renal impairment across a spectrum of ejection fractions and irrespective of diabetic status. Their benefits manifest early after initiation and are sustained over long-term follow-up. Mechanistic studies suggest haemodynamic modulation, favourable effects on myocardial energy metabolism and attenuation of maladaptive neurohormonal activation. Collectively, the evidence supports the integration of SGLT2 inhibitors into standard heart failure regimens, with implications for global health and resource allocation in chronic cardiovascular care.

Research from Nature Portfolio

Recent clinical trials have extended the application of SGLT2 inhibitors to acute settings and remote care models. In a randomised trial of patients hospitalised with acute de novo or decompensated chronic heart failure, initiation of empagliflozin within days of admission led to a significant hierarchical improvement in survival, symptom burden and reductions in recurrent heart failure events over 90 days, regardless of ejection fraction or diabetic status. In a fully remote, patient-centred study, canagliflozin administered without in-person visits produced early and clinically meaningful improvement in heart failure symptom scores at 12 weeks in both preserved and reduced ejection fraction cohorts, underscoring feasibility of virtual trial designs and the broad applicability of SGLT2 therapy.

SGLT2 Inhibitors and Cardiovascular Outcomes in Heart Failure publication trend

The graph below shows the total number of articles in sglt2 inhibitors and cardiovascular outcomes in heart failure across all publications each year (not limited to Nature Index journals).

Technical terms

Sodium–glucose cotransporter 2 (SGLT2) inhibitor: A class of drugs that block glucose reabsorption in the proximal kidney tubule, inducing glycosuria and natriuresis.

Ejection fraction: The percentage of blood ejected from the left ventricle with each heartbeat, used to categorise systolic function.

Composite endpoint: A combined clinical outcome measure that aggregates multiple individual events (e.g. death, hospitalisation) into a single trial endpoint.

Heart failure hospitalisation: Admission to hospital for management of worsening heart failure symptoms or complications.

New York Heart Association (NYHA) functional class: A four-level scale (I–IV) that grades the severity of heart failure symptoms and their impact on daily activities.

References

1. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature Medicine (2022).
2. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nature Medicine (2022).
3. SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis. EClinicalMedicine (2021).
4. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?. Diabetologia (2016).
5. Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction. Circulation (2020).
6. Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction. Circulation (2021).