The heart failure burden of type 2 diabetes mellitus—a review of pathophysiology and interventions

Diabetes and heart failure (HF) are both global epidemics with tremendous costs on society with increased rates of HF hospitalizations and worsened prognosis when co-existing, making it a significant “deadly duo.” The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled trials of HF interventions, usually in patients with reduced ejection fraction (EF), or from subgroup analyses of HF patients recruited to cardiovascular (CV) outcome trials (CVOT) of glucose lowering agents involving patients with T2DM. Studies in patients with HF with preserved EF are sparse. This review summarizes the literature on pathophysiology and interventions aiming to reduce the HF burden in T2DM and includes HF trials of ACEi, digoxin, β-blocker, ARB, I_f-blocker, MRA, and ARNI involving 38,600 patients, with or without prevalent diabetes, and CV outcome trials in T2DM involving 74,351 patients, with or without prevalent HF. In all HF trials, HF outcomes by prevalent diabetes were reported with an incremental risk of HF and death confessed by prevalent diabetes and a treatment effect similar to those without diabetes. All T2DM CVOTs reported on HF outcomes with heterogeneity between trials with two reporting benefits (empagliflozin and canagliflozin) and two reporting increased risk (saxagliptin, pioglitazone). In vulnerable T2DM patients with concomitant HF, guideline-recommended HF drugs are effective. When choosing glucose-lowering therapy, outcomes from available CVOTs should be considered.