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Heart failure and type 2 diabetes: From CVOTs, with hope

Dario Giugliano, Juris J Meier, Katherine Esposito
Diabetes, Obesity & Metabolism 2019 January 4
An excess heart failure (HF) risk persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been so far published, although none, with the exception of DECLARE with dapagliflozin, has included HF in the primary endpoint. The four trials with dipeptidyl-peptidase inhibitors (DPP-4i) (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin that was associated with a 27% increased risk. Five completed CVOTs with the GLP-1 RAs lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), exenatide once weekly (EXSCEL), and albiglutide (HARMONY) also failed to produce any significant effect on HF risk. The three trials with sodium glucose co-transporter-2 inhibitors (SGLT-2i) (EMPA-REG OUTCOME with empagliflozin, CANVAS with canagliflozin, and DECLARE with dapagliflozin) all produced a robust and significant reduction of the Hazard Ratios of hospitalization for HF (from 27% to 35%), which remained consistent, significant, and of similar magnitude regardless of the presence of a history of HF or established atherosclerotic cardiovascular disease. There is no association between reductions of HF risk and haemoglobin A1c (A1C) levels, while there is a significant association between reductions of HR for MACE and A1C levels (Spearman's correlation, r = 0.695, P = 0.013). All the 12 CVOTs so far completed have given reassurance of overall cardiovascular safety of the newer antihyperglycaemic drugs. At present, the robust, consistent and reproducible reduction of about 30% risk of HF by SGLT-2i may be considered a class effect. The beneficial effect on MACE outcome observed with the use of some GLP-1RAs and SGLT-2i must be interpreted within the frame of the single trial. This article is protected by copyright. All rights reserved.


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