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

Abstract

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.