Glucose-lowering drugs and heart failure: implications of recent cardiovascular outcome trials in type 2 diabetes

Heart failure (HF) is common in Type-2 diabetes mellitus (T2DM), and viceversa, leading to a mutual impact on prognosis. Knowledge about this complex interplay has dramatically changed recently, due to development of new glucose-lowering drugs, and to specific FDA and EMA Guidance mandating to perform cardiovascular outcome trials (CVOTs), aimed at establishing cardiovascular safety, for new anti-diabetic treatments before they enter the market. Such CVOTs have demonstrated that the effects of the new antidiabetic drugs on the mutual interactions between T2DM and HF may develop across different phases: BEFORE HF ONSET (PRIMARY PREVENTION): evidence of benefit in preventing HF in T2DM (direct data) WHEN HF IS ALREADY PRESENT (SECONDARY PREVENTION): evidence of benefits in T2DM patients with HF (subgroup analysis data). Results of such trials can be summarized as: (a) all different classes of novel glucose-lowering drugs have good cardiovascular safety profile; (b) with respect to HF, DPP4 inhibitors might tend to increase risk; (c) sodium-glucose co-transporter 2 inhibitors (SGTLi), significantly reduce it; (d) glucagon-like peptide 1 receptor agonists (GLP1) tend to be neutral. These CVOTs data have led to guideline recommendations indicating appropriate therapy to T2DM patients with HF not at glycemic control target with metformin therapy. (C) 2019 Published by Elsevier B.V.