Internal and emergency medicineAug 20, 2026

Oral semaglutide compared to DPP-4 inhibitors for lowering risk of thinking problems in older adults with heart failure and obesity

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 21, 2026

Abstract

At one-year follow-up, 106 new cases of cognitive impairment were observed among 246 elderly patients with heart failure, obesity, and type 2 diabetes.

The overall incidence of cognitive impairment was 43.1 events per 100 patients per year.
Patients treated with oral semaglutide experienced 26.8 events per 100 patients per year.
In contrast, those receiving DPP-4 inhibitors had 59.3 events per 100 patients per year.
A significant difference in cognitive impairment incidence was noted between the two treatment groups (p<0.0001).
Logistic regression analysis suggested a 77% reduced risk of cognitive impairment for patients on oral semaglutide compared to those on DPP-4 inhibitors.

Simplified

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.

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Oral semaglutide compared to DPP-4 inhibitors for lowering risk of thinking problems in older adults with heart failure and obesity

Abstract

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