Insulin treatment in patients with diabetes mellitus and heart failure in the era of new antidiabetic medications

BACKGROUND: Coexistent heart failure (HF) and diabetes mellitus (DM) are associated with marked morbidity and mortality. Optimizing treatment strategies can reduce the number and severity of events. Insulin is frequently used in these patients, but its benefit/risk ratio is still not clear, particularly since new antidiabetic drugs that reduce major adverse cardiac events (MACEs) and renal failure have recently come into use. Our aim is to compare the clinical effects of insulin in a real-world setting of first-time users, with sodium-glucose cotransporter-2 inhibitor (SGLT-2i), glucagon-like peptide-1 receptor agonist (GLP-1RA) and the other antihyperglycemic agents (other-AHAs). METHODS: We used the administrative databases of two Italian regions, during the years 2010–2018. Outcomes in whole and propensity-matched cohorts were examined using Cox models. A meta-analysis was also conducted combining the data from both regions. RESULTS: We identified 34 376 individuals ≥50 years old with DM and HF; 42.0% were aged >80 years and 46.7% were women. SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin and particularly death from any cause (SGLT-2i, hazard ratio (95% CI) 0.29 (0.23 to 0.36); GLP-1RA, 0.482 (0.51 to 0.42)) and first hospitalization for HF (0.57 (0.40 to 0.81) and 0.67 (0.59 to 0.76)). CONCLUSIONS: In patients with DM and HF, SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin, and particularly any cause of death and first hospitalization for HF. These groups of medications had high safety profiles compared with other-AHAs and particularly with insulin. The inadequate optimization of HF and DM cotreatment in the insulin cohort is noteworthy.