European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure

Petar M. Seferović*, Andrew J.S. Coats, Piotr Ponikowski, Gerasimos Filippatos, Martin Huelsmann, Pardeep S. Jhund, Marija M. Polovina, Michel Komajda, Jelena Seferović, Ibrahim Sari, Francesco Cosentino, Giuseppe Ambrosio, Marco Metra, Massimo Piepoli, Ovidiu Chioncel, Lars H. Lund, Thomas Thum, Rudolf A. De Boer, Wilfried Mullens, Yuri LopatinMaurizio Volterrani, Loreena Hill, Johann Bauersachs, Alexander Lyon, Mark C. Petrie, Stefan Anker, Giuseppe M.C. Rosano

*Corresponding author for this work

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Abstract

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium–glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.

Original languageEnglish
Pages (from-to)196-213
JournalEuropean Journal of Heart Failure
Volume22
Issue number2
Early online date09 Dec 2019
DOIs
Publication statusPublished - Feb 2020

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Keywords

  • Cardiovascular risk
  • Clinical trial
  • Dipeptidyl peptidase-4 inhibitor
  • Glucagon-like peptide-1 receptor agonist
  • Heart failure
  • Hospitalisation
  • Sodium–glucose co-transporter type 2 inhibitor
  • Type 2 diabetes mellitus

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