Key result
SGLT2i therapy linked to ~20% lower 5-year dementia risk vs DPP-4i in older diabetics.
Why the study?
Patients with T2DM face an increased risk of dementia, and while SGLT2 inhibitors may offer neuroprotective effects beyond glucose control, evidence remains limited.
Does SGLT2i therapy reduce the incidence of dementia in older adults with type 2 diabetes compared to DPP-4i?
Cohort (n=38,140)
Does SGLT2i therapy reduce the incidence of dementia in older adults with type 2 diabetes compared to DPP-4i?
Hazard Ratio: 0.8 (95% CI 0.7–0.93)
Absolute Event Rate: 5.4% vs 6.4%
p-value: p=0.002
In older adults with type 2 diabetes, initiating an SGLT2 inhibitor was associated with a significantly lower 5-year risk of developing dementia compared to initiating a DPP-4 inhibitor.
SGLT2i use was associated with lower dementia incidence vs DPP-4i in older T2DM; leaves open causality and needs confirmation in RCTs.
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of dementia due to hyperglycemia, insulin resistance, and vascular dysfunction. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may have neuroprotective effects beyond glucose control, but evidence remains limited. This study aimed to assess whether SGLT2i use is associated with a lower incidence of dementia compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) in older adults with T2DM. METHODS: This retrospective cohort study used data from the IQVIA™ Disease Analyzer database in Germany. Patients aged ≥60 years with T2DM, receiving metformin and newly prescribed SGLT2i or DPP-4i (2012-2022), were included. Those with prior neurodegenerative diagnoses were excluded. Propensity score matching (1:1) and Cox proportional hazards models were used to estimate hazard ratios (HR) for dementia over five years. RESULTS: After matching, 38,140 patients were included. Dementia incidence was lower in the SGLT2i group (5.4 %) than the DPP-4i group (6.4 %) (p = 0.002). SGLT2i use was linked to a 20 % reduced dementia risk (HR: 0.80; 95 % CI: 0.70-0.93; p = 0.002), especially in patients >80 years (HR: 0.75) and males (HR: 0.77). CONCLUSIONS: SGLT2i therapy was associated with a lower incidence of dementia in older adults with T2DM, particularly in men and the very elderly.
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Sarabhai et al. (2025) conducted a cohort in type 2 diabetes mellitus (n=38,140). SGLT2 inhibitors vs. DPP-4 inhibitors was evaluated on incidence of dementia (HR 0.80, 95% CI 0.70-0.93, p=0.002). SGLT2 inhibitor therapy was associated with a reduced 5-year risk of dementia compared to DPP-4 inhibitors in older adults with type 2 diabetes (HR 0.80; 95% CI 0.70-0.93; p=0.002).
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