Benefits of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide-1 receptor agonists in older patients with type 2 diabetes
4 affiliations
- 1Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA
- 2Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX, USA
- 3Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
- 4John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA
Abstract
Background: 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.
Related
- Sodium-glucose cotransporter 2 inhibitors vs. glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for incident and recurrent urolithiasis: a European Association of Urology Endourology systematic review
- Effects of Renin–Angiotensin Inhibitors, Sodium–Glucose Cotransporter 2 Inhibitors, Mineralocorticoid Receptor Antagonists and Glucagon‐Like Peptide 1 Receptor Agonists on Kidney Outcomes in Patients With Type 1 Diabetes: A Systematic Review and Meta‐Analysis
- Association of Glucagon-like Peptide-1 Receptor Agonists Versus Dipeptidyl Peptidase-4 Inhibitors with Tuberculosis and Mortality in Adults with Diabetes
- Glucagon-like peptide-1 receptor agonists beyond weight loss: A paradigm shift in cardiovascular prevention
- Divergent ocular safety profiles of glucagon-like peptide-1 receptor agonists: a pharmacological heterogeneity framework
BibTeX
@article{mortada2026benefits,
title = {{Benefits of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide-1 receptor agonists in older patients with type 2 diabetes}},
author = {Ibrahim Mortada and Krishna Paul and James Rice and Noah Joseph and Trevor L. Raum and Mohanad Albayyaa and Diann Gaalema and Dietrich Jehle and Thomas A. Blackwell and Hani Jneid},
journal = {Diabetes \& Vascular Disease Research},
year = {2026},
month = sep,
doi = {10.1177/14791641261495569},
url = {https://doi.org/10.1177/14791641261495569},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Benefits of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide-1 receptor agonists in older patients with type 2 diabetes
AU - Ibrahim Mortada
AU - Krishna Paul
AU - James Rice
AU - Noah Joseph
AU - Trevor L. Raum
AU - Mohanad Albayyaa
AU - Diann Gaalema
AU - Dietrich Jehle
AU - Thomas A. Blackwell
AU - Hani Jneid
PY - 2026
DA - 2026/09/29
JO - Diabetes & Vascular Disease Research
DO - 10.1177/14791641261495569
UR - https://doi.org/10.1177/14791641261495569
AB - Background: 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.
SN - 1479-1641
SN - 1752-8984
ER -