Internal and emergency medicineJul 23, 2026

Semaglutide's effects on thinking skills in people with type 2 diabetes and mild memory problems over 24 months

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 24, 2026

Abstract

Semaglutide treatment was associated with a significant median improvement of 4 points in cognitive performance after 24 months in adults with type 2 diabetes and mild cognitive impairment.

Significant reductions in body weight, BMI, waist circumference, fasting glucose, and HbA1c were observed with semaglutide treatment (all p < 0.05).
Cognitive performance, measured by the Montreal Cognitive Assessment (MoCA), improved substantially at the end of the study compared to baseline.
At the end of the study, semaglutide recipients had higher MoCA scores than the control group (+4.0 vs -1.5, p < 0.001).
Improvements in cognitive tests included the Digit Symbol Substitution Test (DSST) and Beck Depression Inventory (BDI) scores, with p-values of 0.001 and 0.044, respectively.
No patients treated with semaglutide progressed to dementia, whereas 14 patients in the control group did (p = 0.002).
Differences in cognitive improvement between semaglutide formulations may indicate varying effects on the central nervous system.

Simplified

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of mild cognitive impairment (MCI) and dementia. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide cardiovascular and metabolic benefits, and emerging data suggest neurocognitive effects. We conducted a 24-month prospective observational study of 72 adults (≥ 50 years) with T2DM and MCI treated with semaglutide (subcutaneous [SC] or oral) and assessed at baseline (T0) and every 6 months (T1-T4). Outcomes included anthropometrics, fasting glucose, HbA1c, LDL-c, and neuropsychological tests (Montreal Cognitive Assessment [MoCA], Digit Symbol Substitution Test [DSST], Beck Depression Inventory [BDI]). A control cohort of 60 patients with T2DM and MCI not receiving semaglutide was evaluated with the same protocol. Semaglutide was associated with significant reductions in body weight, BMI, waist circumference, fasting glucose, and HbA1c (all p < 0.05). Cognitive performance improved, as shown by MoCA scores (median Δ≈ + 4 points, p < 0.001) at T4 compared with T0; at T4, semaglutide recipients also had higher MoCA scores than controls (+ 4.0 vs - 1.5, p < 0.001). DSST and BDI scores also improved (p = 0.001 and p = 0.044, respectively). MoCA improved similarly with both formulations, whereas DSST improvement reached significance only with SC semaglutide. In multivariable regression, semaglutide independently predicted MoCA improvement (+ 4.76 points, p < 0.001). No semaglutide-treated patient progressed to dementia versus 14 in controls (p = 0.002). In adults with T2DM and MCI, semaglutide was associated with improved cognition and a lower risk of progression to dementia. Differences between formulations may reflect distinct central nervous system engagement. Randomized trials are warranted.