Benefits of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide-1 receptor agonists in older patients with type 2 diabetes
Ibrahim Mortada, Krishna Paul, James Rice, Noah Joseph, Trevor L. Raum, Mohanad Albayyaa, Diann Gaalema, Dietrich Jehle, Thomas A. Blackwell, Hani JneidBackground
Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular and neurocognitive complications. GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2is) have pleiotropic effects beyond glycemic control, but comparative long-term data on dementia, cardiovascular events, and mortality in older adults are limited.
Methods
This retrospective cohort study used the TriNetX US Collaborative Network. Adults ≥60 years with T2DM on metformin plus either GLP-1 RAs or SGLT2is (n=56,211 per cohort after matching, 2014–2020) were propensity-score matched on demographic and clinical characteristics. Five-year outcomes included incident Alzheimer’s disease, vascular dementia, other dementia, dementia-related medication use, NSTEMI, STEMI, and all-cause mortality.
Results
After propensity-score matching, GLP-1 RA use was associated with higher risks of Alzheimer’s disease (RR 1.33, 95% CI 1.18–1.48), vascular dementia (RR 1.56, 95% CI 1.39–1.76), other dementia (RR 1.33, 95% CI 1.21–1.47), dementia-related medication initiation, and all-cause mortality (RR 1.11, 95% CI 1.08–1.15) compared with SGLT2is. NSTEMI and STEMI risks did not differ significantly between groups.
Conclusions
In older adults with T2DM, SGLT2is were associated with lower risks of dementia, dementia-related medication use, and all-cause mortality compared with GLP-1 RAs in propensity-score matched cohorts. These observational findings are hypothesis-generating and should be confirmed in prospective studies.