SGLT2 Inhibitors May Shield Against Dementia in Older Adults with Type 2 Diabetes: Study Suggests
Germany: Older adults with type 2 diabetes mellitus (T2DM) who receive sodium-glucose cotransporter-2 inhibitors (SGLT2i) may have a lower risk of developing dementia compared to those on dipeptidyl peptidase-4 inhibitors (DPP-4i), according to a large real-world study published in Diabetes Research and Clinical Practice.
The research was conducted by Theresia Sarabhai and colleagues from the Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Germany.
T2DM significantly increases the likelihood of dementia due to persistent hyperglycemia, insulin resistance, and vascular complications. While SGLT2 inhibitors are primarily prescribed for glycemic control and cardiovascular protection, emerging evidence suggests they may also provide neuroprotective benefits.
To explore this association, researchers analyzed data from the IQVIA Disease Analyzer database in Germany. The retrospective cohort included 38,140 adults aged 60 years and above who had T2DM, were on metformin, and started treatment with either SGLT2 inhibitors or DPP-4 inhibitors between 2012 and 2022. Patients with prior neurodegenerative conditions were excluded. Propensity score matching (1:1) and Cox proportional hazards models were used to adjust for potential confounders and estimate hazard ratios (HR) over five years.
The analysis revealed the following findings:
- The incidence of dementia was significantly lower among SGLT2 inhibitor users (5.4%) compared to DPP-4 inhibitor users (6.4%).
- SGLT2i therapy was linked to a 20% reduction in the risk of all-cause dementia (HR: 0.80).
- The protective effect was more evident in individuals aged over 80 years (HR: 0.75) and in male patients (HR: 0.77).
- The benefit was mainly observed for unspecified dementia, with no significant difference in the risk of Alzheimer’s disease or vascular dementia.
These findings suggest that SGLT2 inhibitors could play a role beyond glucose control, potentially mitigating cognitive decline in older adults with diabetes. Given that dementia is a growing global health concern, such benefits could have far-reaching implications for diabetes management strategies. The authors emphasized that while observational data provide valuable insights, randomized controlled trials are needed to confirm these neuroprotective effects and to understand underlying mechanisms.
They suggest that further research should also consider long-term cognitive outcomes, age- and sex-specific responses, and explore whether SGLT2 inhibitors directly influence neurodegenerative pathways.
"The study adds to the growing body of evidence supporting the broader benefits of SGLT2 inhibitors, which are already recognized for their cardiovascular and renal advantages. For older patients with T2DM who face an elevated risk of dementia, these drugs might offer an additional protective edge, potentially shaping future guidelines for comprehensive diabetes care," the authors concluded.
Reference:
Sarabhai, T., Zingel, R., Bohlken, J., & Kostev, K. (2025). Association between SGLT2 inhibitor therapy and prolonged dementia-free survival in older adults with type 2 diabetes: A retrospective cohort study from Germany. Diabetes Research and Clinical Practice, 112430. https://doi.org/10.1016/j.diabres.2025.112430
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