GLP-1 receptor agonists and heart failure in diabetes
Abstract
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14),…
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