Heart failure outcomes in clinical trials of glucose-lowering agents in patients with diabetes

Diabetes is a major risk factor for heart failure (HF). Patients with diabetes have a high incidence of both clinical HF and subclinical LV dysfunction. Although intensive glucose lowering does not appear to impact on HF outcomes, the choice of glucose-lowering agents plays an important role in the development of HF and related cardiovascular outcomes. Whilst metformin and insulin appear to have little impact on HF progression, the role of sulphonylurea agents in this patient population remains uncertain. Thiazolidinediones (TZDs) are associated with a significant risk of HF progression and are best avoided in patients at risk. The incretin-based therapies (GLP agonists and DPP-4 inhibitors) are generally not associated with any HF interaction. However, a small increase in HF admissions was observed with the DPP-4 inhibitor saxagliptin. The GLP-1 agonist liraglutide was recently shown to reduce cardiovascular and all-cause mortality, yet hospitalization for HF was not significantly reduced. The SGLT2 inhibitor empagliflozin was shown to reduce HF admissions and cardiovascular mortality in patients with prior cardiovascular disease including HF. These recent data showing improved outcomes with a glucose-lowering category provide a novel strategy to improve survival and reduce morbidity in diabetic patients at high cardiovascular disease risk.