Comparative effectiveness of sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists for incident dementia: A retrospective multicohort study

Objective This study provides real‐world evidence on the comparative effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) regarding the risk of incident dementia in adults with type 2 diabetes mellitus (T2DM). Research Design and Methods This cohort study utilised electronic health records from TriNetX (1 April 2013 to 31 December 2019). Adults with T2DM on metformin who initiated GLP‐1 RAs or SGLT2i were analysed using Cox proportional hazards models in 1:1 propensity score‐matched cohorts. The primary outcome was all‐cause dementia; secondary outcomes included vascular and Alzheimer's dementia. Confounding variables were adjusted. Results Among 16 271 participants using GLP‐1 RAs and 16 271 using SGLT2i over a median 6.3‐year follow‐up, 581 GLP‐1 RA users and 572 SGLT2i users developed dementia. No significant differences were observed in all‐cause dementia (hazard ratio: 1.01, 95% confidence interval: 0.90–1.13), vascular, or Alzheimer's dementia. Subgroup analyses confirmed these findings. Conclusions SGLT2i use was not associated with increased risk of dementia compared with GLP‐1RAs in patients with T2DM. Further research is warranted to explore the effects of (newer) incretin‐based (co‐)agonists on cognitive outcomes.