GLP-1 receptor agonists were associated with a 24% lower dementia risk than DPP4 inhibitors (HR 0.76) but a 53% higher risk than SGLT2 inhibitors (HR 1.53) in older adults with T2D.
Does initiation of GLP-1 receptor agonists reduce incident dementia in older adults with type 2 diabetes compared to DPP4 inhibitors or SGLT2 inhibitors?
In older adults with type 2 diabetes, GLP-1 receptor agonists are associated with a lower risk of incident dementia compared to DPP4 inhibitors, but a higher risk compared to SGLT2 inhibitors.
Tasa de eventos absoluta: 0% vs 0%
Abstract Aim Type 2 diabetes (T2D) is associated with increased dementia risk, but comparative data across newer glucose‐lowering therapies remain limited. We examined whether the initiation of GLP‐1 receptor agonists (GLP‐1 RAs) was associated with incident dementia compared with DPP4 inhibitors (DPP4is) and SGLT2 inhibitors (SGLT2is) in older adults with T2D. Materials and methods We conducted a retrospective cohort study emulating a target trial using electronic health records from the University of Pennsylvania Health System (2019–2024), with external validation in the TriNetX U.S. Collaborative Network. Adults aged ≥50 with T2D, no prior dementia, and no GLP‐1 RA, DPP4i, or SGLT2i use in the previous year were eligible. New GLP‐1 RA users were propensity‐score matched (1:1) to DPP4i users ( n = 6677 pairs) and SGLT2i users ( n = 8434 pairs). The outcome was incident dementia, defined by ICD‐10‐CM codes. Cox proportional hazards models estimated hazard ratios (HRs), with multiple sensitivity and subgroup analyses performed. Results Over a median follow‐up of 3.0 years (GLP‐1 RA vs. DPP4i) and 2.4 years (GLP‐1 RA vs. SGLT2i), GLP‐1 RA use was associated with a lower dementia risk versus DPP4is (109 vs. 148 events; HR 0.76, 95% CI 0.59–0.97), but a higher risk versus SGLT2is (127 vs. 64 events; HR 1.53, 95% CI 1.13–2.07). Findings were consistent across sensitivity and subgroup analyses. External validation confirmed reduced dementia risk versus DPP4is but not versus SGLT2is. Conclusions In this large real‐world cohort, GLP‐1 RAs were associated with lower dementia risk than DPP4is but higher risk than SGLT2is. Prospective, biomarker‐informed studies are needed to clarify mechanisms and inform treatment choices in older adults with T2D.
Zhou et al. (Mon,) reported a other. GLP-1 receptor agonists were associated with a 24% lower dementia risk than DPP4 inhibitors (HR 0.76) but a 53% higher risk than SGLT2 inhibitors (HR 1.53) in older adults with T2D.