In a large matched study, people with type 2 diabetes had the same dementia risk whether they took a GLP-1 receptor agonist or an SGLT2 inhibitor over a median 6.3-year follow-up.
HR 1.01No difference in dementia risk between GLP-1 RAs and SGLT2 inhibitors over 6.3 years
What the researchers found
GLP-1 receptor agonists and SGLT2 inhibitors showed equivalent dementia risk (HR 1.01, 95% CI 0.90–1.13) in propensity-matched diabetic adults.
Why it matters
As both drug classes gain wider use, this study reassures patients and clinicians that choosing between GLP-1 RAs and SGLT2 inhibitors need not be driven by dementia concerns—neither appears riskier for cognitive decline.
How the study worked
Retrospective cohort study using TriNetX electronic health records (2013–2019) with 1:1 propensity score matching and Cox proportional hazards models.
What this study cannot tell us
Retrospective design limits causal inference. The study could not account for duration or dosing of therapy, and newer agents like tirzepatide were not assessed.
How to read the evidence
Large real-world cohort with robust propensity matching, though retrospective design and potential residual confounding limit certainty.
When this study was published
Published in 2026 using data from 2013–2019.
The bigger picture
Both GLP-1 RAs and SGLT2 inhibitors have shown neuroprotective signals in preclinical work. This head-to-head real-world comparison suggests neither has a clear cognitive advantage, leaving the choice to be guided by cardiovascular, renal, and metabolic priorities.
Questions still open
- Would newer dual or triple agonists (e.g., tirzepatide, retatrutide) show different cognitive outcomes?
- Does the neuroprotective benefit of either class become clearer with follow-up beyond six years?
- Could certain patient subgroups (e.g., those with pre-existing cognitive impairment) respond differently to one class?
Common questions
Do GLP-1 drugs protect against dementia?
Should I choose my diabetes medication based on dementia risk?
Read the original research
Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study.
Diabetes, obesity & metabolism, 28(2), 1443-1452
Citation
Anagnostakis, Filippos; Kokkorakis, Michail; Nagarajan, Shrihari; Anastasiou, Georgia; Mantzoros, Christos S. (2026). Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study.. Diabetes, obesity & metabolism, 28(2), 1443-1452. https://doi.org/10.1111/dom.70336