T2DM is a well-recognized risk factor for dementia due to hyperglycemia, insulin resistance, and vascular dysfunction. A retrospective cohort study published in Diabetes Research and Clinical Practice, evaluated whether SGLT2i reduce dementia risk compared with DPP-4i using the IQVIA™ in older adults with T2DM.

The analysis used a large German outpatient healthcare database and included 38,140 patients aged 60 years and older with T2DM who were receiving metformin and newly prescribed either SGLT2i or DPP-4i between 2012 and 2022. Patients with prior neurodegenerative diagnoses were excluded. Propensity score matching (1:1) and Cox proportional hazards models were applied to estimate dementia risk over five years.

Dementia incidence was significantly lower in the SGLT2i group (5.4%) compared with the DPP-4i group (6.4%; P = 0.002). SGLT2i therapy was associated with a 20% risk reduction (HR 0.80; 95% CI 0.70–0.93; P = 0.002). Subgroup analysis showed the strongest protective effect in men (HR 0.77) and in those aged over 80 years (HR 0.75).

These findings suggest SGLT2i therapy use may provide cognitive benefits beyond glycemic control, although further prospective studies are warranted.highlighting the need for prospective studies to confirm causality.