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To review the evidence for sodium-glucose cotransporter 2 inhibitors (SGLT2i) for the prevention of heart failure in patients with type 2 diabetes.
To review the evidence for SGLT2i as a treatment for heart failure and reduced ejection fraction (HFrEF) irrespective of diabetes status.
To understand which patients with HFrEF are eligible for treatment with an SGLT2i and review some practical tips for the implementation of SGLT2i into clinical practice.
Despite advances in both the pharmacological and the device-based management of heart failure with reduced ejection fraction (HFrEF), patients remain at a high risk of morbidity and mortality. The last decade has seen a new era in the pharmacological management of HFrEF with four drug classes affecting five distinct physiological pathways now established as cornerstones of HFrEF pharmacotherapy: an angiotensin receptor-neprilysin inhibitor (ARNI) in the form of sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists (MRA) and, most recently, sodium-glucose cotransporter 2 inhibitors (SGLT2i). Originally investigated as glucose-lowering agents, SGLT2i in randomised, placebo-controlled trials prevented the development of heart failure (HF) in patients with type 2 diabetes with established or at high risk of cardiovascular disease.1–5 The clinical benefits of SGLT2i were independent of their glucose-lowering effect. Subsequently, two large, randomised, placebo-controlled trials have reported that SGLT2i (dapagliflozin and empagliflozin) improved morbidity and mortality in patients with HFrEF, irrespective of diabetes status.6 7 A further trial has reported on the benefits of sotagliflozin, a combined SGLT1 and SGLT2 inhibitor, in patients with diabetes and hospitalised HF.8 The purpose of this article is to provide background on the use of SGLT2i in patients with HF, review the evidence for their use, suggest how they may be implemented in clinical practice as a new cornerstone in the management of patients with HFrEF and discuss ongoing trials of SGLT2i across the HF landscape.
Sodium-glucose cotransporter-2 inhibitors
Twitter @Kieranfdocherty, @markcpetrie20
Contributors Both authors contributed equally to this manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests KFD reports that his employer, the University of Glasgow, has been rumunerated by AstraZeneca for his work relating to the DAPA-HF trial and he has received honoraria from AstraZeneca and Eli Lilly. MCP reports research support or consultancy from Boehringer Ingelheim, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Vifor, Pharmacosmos, AbbVie, Bayer, Takeda, Cardiorentis and Siemens. MCP is supported by The British Heart Foundation grant RE/18/6/34217.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note References which include a * are considered to be key references.