Heart failure considerations of antihyperglycemic medications for type 2 diabetes

Eberhard Standl, Oliver Schnell, Darren K. McGuire

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Prevalent and incident heart failure (HF) is increased in people with type 2 diabetes mellitus, with risk directly associated with the severity of hyperglycemia. Furthermore, in patients with type 2 diabetes mellitus, mortality is increased ≈10-fold in patients with versus without HF. Reducing HF with antihyperglycemic therapies, however, has been unsuccessful until recently. In fact, HF as an important outcome in patients with type 2 diabetes mellitus seems to be heterogeneously modulated by antihyperglycemic medications, as evidenced by results from cardiovascular outcome trials (CVOTs) and large observational cohort studies. Appropriately powered and executed CVOTs are necessary to truly evaluate cardiovascular safety and efficacy of new antihyperglycemic medications, as reflected by the guidance of the US Food and Drug Administration and other regulatory agencies since 2008. In light of the best available evidence at present, metformin and the sodium-glucose-co-transporter 2-inhibitor empagliflozin seem to be especially advantageous with regard to HF effects, with their use associated with reduced HF events and improved mortality. Acarbose, the dipeptidyl-peptidase 4-inhibitor sitagliptin, the glucagon-like peptide 1-receptor agonist lixisenatide based on presently available CVOT results comprise reasonable additional options, as significant harm in terms of HF has been excluded for those drugs. Additions to this list are anticipated pending results of ongoing CVOTs. Although no HF harm was seen in CVOTs for insulin or sulfonylureas, they should be used only with caution in patients with HF, given their established high risk for hypoglycemia and some uncertainties on their safety in patients with HF derived from epidemiological observations. Pioglitazone is contraindicated in patients with HF>New York Heart Association I, despite some benefits suggested by CVOT subanalyses.

Original languageEnglish (US)
Pages (from-to)1830-1843
Number of pages14
JournalCirculation Research
Volume118
Issue number11
DOIs
StatePublished - May 27 2016

Keywords

  • antihyperglycemic agents
  • cardiovascular disease
  • diabetes mellitus, type 2
  • heart failure

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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