Abstract
In the Netherlands, approximately 250,000 people are living with heart failure. About one-third of them have comorbid diabetes mellitus type 2. Until recently, the effects of antidiabetic agents on heart failure were largely unknown. This changed after an observed increased risk of heart failure and ischaemic heart disease associated with thiazolidinediones that prompted the requirement for cardiovascular outcome trials for new glucose-lowering drugs. In the past decade, three new classes of antidiabetic agents have become available (i.e. dipeptidyl peptidase‑4 inhibitors, glucagon-like peptide‑1 receptor agonists and sodium-glucose cotransporter‑2 (SGLT2) inhibitors). Although the first two classes demonstrated no beneficial effects on heart failure compared to placebo in patients with diabetes mellitus type 2, SGLT2 inhibitors significantly and consistently lowered the risk of incident and worsening heart failure. Two recent trials indicated that these favourable effects were also present in non-diabetic patients with heart failure with reduced ejection fraction, resulting in significantly lower risks of hospitalisation for heart failure and presumably also cardiovascular and all-cause mortality. SGLT2 inhibitors have been shown to be benefit on top of recommended heart failure therapy including sacubitril/valsartan and may also prove beneficial for heart failure with preserved ejection fraction. In this review, we discuss the effects of antidiabetic agents on heart failure.
Highlights
In the Netherlands, approximately 250,000 people are living with heart failure [1]
The effects of antidiabetic agents on heart failure were largely unknown. This changed after an observed increased risk of incident and worsening heart failure, as well as ischaemic heart disease associated with thiazolidinediones that prompted the requirement for cardiovascular outcome trials for new glucose-lowering drugs in 2008 [7]
The choice of metformin as a first-line antidiabetic agent has largely relied on encouraging results on cardiovascular risk reduction observed in the UKPDS (United Kingdom Prospective Diabetes Study) [9]
Summary
In the Netherlands, approximately 250,000 people are living with heart failure [1]. The term heart failure describes the signs and symptoms of underlying heart disease that results in elevated cardiac pressures or reduced cardiac output, regardless of aetiology, and is mainly subdivided according to left ventricular ejection fraction (LVEF) into heart failure with reduced (LVEF ≤ 40%), mid-range (LVEF 41–49%) and preserved (LVEF ≥ 50%) ejection fraction (HFrEF, HFmrEF and HFpEF) [2]. Most studies on heart failure have focused on HFrEF and, to a lesser extent, HFpEF. Diabetes mellitus type 2 is a frequent cause and comorbidity in patients with heart failure, affecting approximately one-third of the patient population [3]. Prognosis of heart failure is worse in patients with compared to those without diabetes mellitus type 2. This is illustrated by a recent meta-analysis that included data from 381,275 individuals with heart failure that demonstrated a significantly increased risk of all-cause mortality (hazard ratio (HR) 1.28 (95% confidence interval (CI) 1.21–1.35)), cardiovascular mortality (HR 1.34 (95% CI 1.20–1.49)) and hospitalisation for heart failure (HR 1.35 (95% CI 1.20–1.50)) associated with diabetes mellitus type 2 [6]
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