Clinical implications of cardiovascular outcome trials in type 2 diabetes

Abstract

Cardiovascular disease (CVD) is the main reason for premature death in patients with type 2 diabetes. Hyperglycemia, the hallmark of diabetes, has long been considered the link between diabetes and CVD, and many trials focused on preventing CVD manifestations by means of tight glucose control. However, diabetes is a multifactorial disease in which, e. g., insulin resistance, endothelial dysfunction, and factors such as hypertension and dyslipidemia contribute. Thus, treatment needs to be multifactorial and take cardiovascular aspects into account. Newer classes of drugs, originally launched for glucose lowering, among them dipeptidyl-peptidase (DPP)-4 inhibitors, sodium-glucose cotransporter (SGLT)-2 inhibitors, and glucagon-like peptide (GLP)-1 receptor agonists, have been studied in large cardiovascular outcome trials (CVOT). Several SGLT-2 inhibitors and GLP-1 receptor agonists are associated with a reduction of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). Although the mechanisms behind the effects are not fully understood, an important reason for the benefits of SGLT-2 inhibitors seems be a reduction in heart failure, while GLP-1 receptor agonists may retard the development of the atherosclerotic vascular disease or may be effective by stabilizing plaques. The outcomes of these studies have been taken into account in recently issued guidelines and an important task for diabetologists, cardiologists, and general practitioners is to incorporate the findings of these trials into clinical practice.

Keywords: Cardiac diseases; Diabetes mellitus, adult-onset; Dipeptidyl-peptidase 4 inhibitors; Glucagon-like peptide 1 receptor agonists; Sodium–glucose cotransporter 2 inhibitors.

Fig. 1

The impact of the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (a) and the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide (b) on the primary outcome in the EMPA-REG outcomes and LEADER trials, respectively. Both reduced the rates of cardiovascular death or non-fatal myocardial infarction or stroke to a similar extent (relative reduction 14% and 13%, respectively). This outcome was, however, driven by different event reductions and appeared faster with empagliflozin than with liraglutide. CI confidence interval, CV cardiovascular, HR hazard ratio, MI myocardial infarction. (Modified after [39] and [45]. See text for further explanation)