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

Q: What are the key findings of this study?

Oral semaglutide was associated with a 77% reduced risk of incident cognitive impairment compared to DPP-4 inhibitors in elderly patients with HFpEF, obesity, and type 2 diabetes (OR 0.231).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with preserved ejection fraction (HFpEF), obesity, and type 2 diabetes (n=246). Intervention: Oral semaglutide vs. DPP-4 inhibitors. Primary outcome: Incidence of cognitive impairment (MoCA score <26 points) (OR 0.231, 95% CI 0.113-0.474, p=<0.0001).

Q: What does this research mean for the field?

Oral semaglutide is associated with a 77% reduced risk of incident cognitive impairment compared to DPP-4 inhibitors in elderly patients with HFpEF, obesity, and type 2 diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the effects of one-year treatment with oral semaglutide versus DPP-4 inhibitors on the incidence of cognitive impairment in elderly patients with HFpEF, obesity, and type 2 diabetes.

Giuseppe Armentaro; Cristiana Vitale; Velia Cassano; Marilisa Panza; Ilaria Gareri; Maria Mirabelli; Elena Succurro; Francesco Andreozzi; Antonio Brunetti; Gianluigi Savarese; Maurizio Volterrani; Giorgio Sesti; Giuseppe Rosano; Angela Sciacqua

doi:10.1007/s11739-026-04499-4

August 20, 2026Internal and Emergency MedicineOpen Access

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

View Full Paper

Ask AI

Bookmark

Share

Key result

Oral semaglutide is linked to ~77% lower cognitive impairment risk vs DPP4i in diabetic HFpEF.

OR 0.231
95% CI 0.113-0.474
P<0.0001
n=246

Why the study?

HFpEF, obesity, and type 2 diabetes mellitus are common in elderly patients and increase the risk of cognitive impairment, but the comparative effect of oral semaglutide versus DPP-4 inhibitors on this outcome was not established.

Does oral semaglutide reduce the incidence of cognitive impairment in elderly patients with HFpEF, obesity, and type 2 diabetes compared to DPP-4 inhibitors?

Key Points

To evaluate the effects of one-year treatment with oral semaglutide versus DPP-4 inhibitors on the incidence of cognitive impairment in elderly patients with HFpEF, obesity, and type 2 diabetes.
Cohort study analyzing 246 elderly outpatients with HFpEF, obesity, and type 2 diabetes drawn from the MAGIC-HF and CATAMERI registries.
Participants were matched for age, sex, and BMI into two treatment groups receiving oral semaglutide or DPP-4 inhibitors as an add-on hypoglycaemic therapy.
Patients underwent cognitive evaluation using the Montreal Cognitive Assessment (MoCA) at baseline and after a one-year follow-up.
Incident cognitive impairment occurred in 33 patients receiving oral semaglutide (26.8 events/100 patients/year) versus 73 patients receiving DPP-4 inhibitors (59.3 events/100 patients/year, p<0.0001).
Multivariate logistic regression demonstrated a 77% reduced risk of incident cognitive impairment with oral semaglutide compared to DPP-4 inhibitors (OR 0.231, 95% CI 0.113–0.474; p<0.0001).
Oral semaglutide induced greater reductions in BMI (−2.9 kg/m2 vs. −0.7 kg/m2, p<0.0001) and hs-CRP (−1.3 mg/l vs. −0.6 mg/l, p<0.0001), both of which significantly correlated with lower cognitive impairment incidence.

Study Design

Type

Cohort (n=246)

Multicenter

Yes

Structured PICO

Does oral semaglutide reduce the incidence of cognitive impairment in elderly patients with HFpEF, obesity, and type 2 diabetes compared to DPP-4 inhibitors?

P

Population

246 elderly outpatients (mean age 79.5 years, 31.7% female) with HFpEF, obesity, and type 2 diabetes, already on SGLT2i therapy, followed for one year.

E

Exposure

Oral semaglutide (started at 3 mg/day, up-titrated to 7 mg/day or 14 mg/day) added to background hypoglycaemic therapy for one year.

C

Comparator

DPP-4 inhibitors (any agent except saxagliptin) added to background hypoglycaemic therapy for one year.

O

Outcome

Incidence of cognitive impairment (CoI), defined as a Montreal Cognitive Assessment (MoCA) score of <26 points at one-year follow-up.surrogate

Main Result

Odds Ratio: 0.231 (95% CI 0.113–0.474)

Absolute Event Rate: 26.8% vs 59.3%

p-value: p=<0.0001

In elderly patients with HFpEF, obesity, and type 2 diabetes, oral semaglutide significantly reduced the risk of incident cognitive impairment compared to DPP-4 inhibitors over one year.

Limitations

Not a randomized clinical trial
Relatively small sample size

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Hypothesis-generating for cognitive benefit of oral semaglutide in elderly HFpEF; prospective RCTs needed before practice change.

Abstract

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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Armentaro et al. (2026) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF), obesity, and type 2 diabetes (n=246). Oral semaglutide vs. DPP-4 inhibitors was evaluated on Incidence of cognitive impairment (MoCA score <26 points) (OR 0.231, 95% CI 0.113-0.474, p=<0.0001). Oral semaglutide was associated with a 77% reduced risk of incident cognitive impairment compared to DPP-4 inhibitors in elderly patients with HFpEF, obesity, and type 2 diabetes (OR 0.231).

synapsesocial.com/papers/6a895eeeca7ade938187d1d2 https://doi.org/10.1007/s11739-026-04499-4

View Full Paper

Ask AI

Bookmark

Share

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading