The emerging role of novel antihyperglycemic agents in the treatment of heart failure and diabetes: A focus on cardiorenal outcomes

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two global pandemics, affecting over 25 and 420 million people, respectively. The prevalence of comorbid HF and T2DM is rising, and the prognosis remains poor. One central area of overlap of these two disease processes is renal dysfunction, which contributes to poor cardiovascular outcomes and mortality. As such, there is a growing need for antihyperglycemic agents with cardio- and renoprotective effects. Three classes of novel antihyperglycemic agents, sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 (DPP4) inhibitors have demonstrated varied cardiorenal outcomes in recent cardiovascular outcomes trials. Understanding the differential effects of these agents, together with their proposed mechanisms, is crucial for the development of safe and effective treatment regimens and future pharmacologic targets for HF and T2DM. In this review, we discuss the overlapping pathophysiology of HF and T2DM, summarize outcomes data for the novel antihyperglycemic agents and proposed mechanisms of action, and review how the current evidence informs future management of comorbid HF and T2DM.