Oral semaglutide vs DPP-4 inhibitors in reducing risk of cognitive impairment in elderly patients with HFpEF and obesity

Heart failure with preserved ejection fraction (HFpEF), obesity, type 2 diabetes mellitus are common in elderly patients and are associated with an increased risk of cognitive impairment (CoI). In these patients, the protective metabolic and vascular effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well established. The aim of this study was to evaluate effects of one-year treatment with oral semaglutide versus DPP-4 inhibitors (DPP4i), as an add-on to the hypoglycaemic therapy, on the incidence of CoI in patients with HFpEF, obesity, and type 2 diabetes. 246 elderly outpatients were recruited and divided into two groups (oral semaglutide vs. DPP4i), accurately matched for age, sex, and body mass index (BMI). At one-year follow-up, 106 new cases of CoI were observed in the entire study population (43.1 events/100 patients/year). A significant difference was found between the two groups: 33 cases with oral semaglutide (26.8 events/100 patients/year) versus 73 cases with DPP4i (59.3 events/100 patients/year), p<0.0001. Logistic regression analysis indicated a 77% reduced risk of incident CoI with oral semaglutide compared to DPP4i. In elderly patients with HFpEF, obesity and type 2 diabetes, oral semaglutide seems to have a positive effect in reducing the incidence of cognitive impairment.