Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology

Abstract

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.

Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials

“…HF has been found in 10%‐30% of patients participating in T2DM clinical trials . Although hypertension and coronary artery disease (CAD) are prevalent among patients with T2DM and may lead to HF, the direct effect of diabetes on cardiomyocytes may also play a role in the pathogenesis of HF . This idea is further supported by the notion that T2DM and HF share many pathophysiological pathways, including neuroendocrine dysregulation, oxidative stress, and endothelial dysfunction .…”

“…Although hypertension and coronary artery disease (CAD) are prevalent among patients with T2DM and may lead to HF, the direct effect of diabetes on cardiomyocytes may also play a role in the pathogenesis of HF . This idea is further supported by the notion that T2DM and HF share many pathophysiological pathways, including neuroendocrine dysregulation, oxidative stress, and endothelial dysfunction . Free fatty acid release as a consequence of prolonged hyperglycemia and insulin resistance promotes lipotoxicity and myocardial dysfunction which can result in decreased myocardial contractility and HF, offering a possible therapeutic target for HF .…”

“…They are independent of and precede the development of macrovascular and atherosclerotic vascular disease . Most middle‐aged type 2 diabetic patients develop early‐onset diastolic dysfunction, and this phenomenon is seen even in asymptomatic patients with the absence of clinically manifested vascular disease . Clinical HF is one of the most common CV complications of T2DM, and it may present with either preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF) .…”

“…Clinical HF is one of the most common CV complications of T2DM, and it may present with either preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF) . Moreover, CAD is the major cause of HFrEF in T2DM …”

“…This is particularly relevant in patients with T2DM with concomitant CAD in which each 1% increase in glycosylated hemoglobin (HbA1c) level associates with a 36% increased risk of HF hospitalization . Additionally, HF is a leading cause of hospitalizations among T2DM patients and is an independent predictor of poor prognosis . Mortality is 10 to 12 times higher in T2DM patients who develop HF than in those who do not develop HF …”