SGLT-2 Inhibitors versus GLP-1 Receptor Agonists for Dementia and Depression in Type 2 Diabetes Mellitus: A Meta-Analysis
- 1Endocrinology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People's Republic of China.
- 2Neurology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People's Republic of China.
Abstract
Runzhou Pan,1 Bo Wang,2 Yuzheng Li,1 Huiyun Li,1 Xue Liang,1 Yan Zhang,1 Xiaonan Liu,1 Xiaowei Huang,1 Rongrong Wang,1 Hong Ji,1 Yongcai Zhao11Endocrinology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 2Neurology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Yongcai Zhao, Email [email protected]: The comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on dementia and depression risk in patients with type 2 diabetes mellitus (T2DM) remain unclear. We conducted a meta-analysis to directly compare the incidence of dementia and depression-related outcomes between users of these two drug classes.Methods: A systematic literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception to June 1, 2026. Observational studies reporting quantifiable data on dementia or depression-related events in adults with T2DM were included. Detailed information on study design, age, demographic characteristics, eligibility criteria, outcome definitions, and outcome incidence was extracted. Data were pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses involved sequential exclusion of individual studies. Prespecified subgroup analyses examined effect modifiers including geographic region, study design, age, and follow-up duration. Study quality was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence and methodological rigor of this meta-analysis were evaluated using the AMSTAR 2 checklist.Results: Thirteen observational studies comprising 1,055,315 participants were included. Compared with GLP-1RA users, SGLT-2i users had lower rates of all-cause dementia (OR 0.85, 95% CI 0.77– 0.94; P = 0.001), vascular dementia (OR 0.75, 95% CI 0.71– 0.80; P < 0.001), Alzheimer’s disease (OR 0.76, 95% CI 0.72– 0.79; P < 0.001), and composite depression-related outcomes (OR 0.76, 95% CI 0.67– 0.88; P = 0.001), including suicide/self-harm (OR 0.69, 95% CI 0.60– 0.80; P < 0.001) and depression/anxiety (OR 0.78, 95% CI 0.65– 0.93; P = 0.006). Subgroup analyses revealed more pronounced differences in Asian populations (dementia: OR 0.86, 95% CI 0.75– 0.99; I2 = 0%), European cohorts (depression: OR 0.67, 95% CI 0.54– 0.84; I2 = 83%), and in studies that enrolled younger adults (minimum age 18 years, without an upper age restriction) (dementia: OR 0.79, 95% CI 0.76– 0.81; I2 = 0%; depression: OR 0.67, 95% CI 0.54– 0.84; I2 = 83%).Conclusions: In this meta-analysis of observational studies, SGLT-2i use was associated with lower rates of dementia and depression-related outcomes compared with GLP-1RA use in patients with T2DM. Age and geographic region may influence the observed associations. Future randomized controlled trials and studies reporting outcomes stratified by sex, socioeconomic status, and educational level are warranted.Keywords: sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, depression, dementia, meta-analysis, observational studies
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BibTeX
@article{pan2026sglt2,
title = {{SGLT-2 Inhibitors versus GLP-1 Receptor Agonists for Dementia and Depression in Type 2 Diabetes Mellitus: A Meta-Analysis}},
author = {Runzhou Pan and Bo Wang and Yuzheng Li and Huiyun Li and Xue Liang and Yan Zhang and Xiaonan Liu and Xiaowei Huang and Rongrong Wang and Hong Ji and Yongcai Zhao},
journal = {Diabetes, Metabolic Syndrome and Obesity},
year = {2026},
month = nov,
doi = {10.2147/dmso.s628886},
url = {https://www.dovepress.com/sglt-2-inhibitors-versus-glp-1-receptor-agonists-for-dementia-and-depr-peer-reviewed-fulltext-article-DMSO},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - SGLT-2 Inhibitors versus GLP-1 Receptor Agonists for Dementia and Depression in Type 2 Diabetes Mellitus: A Meta-Analysis
AU - Runzhou Pan
AU - Bo Wang
AU - Yuzheng Li
AU - Huiyun Li
AU - Xue Liang
AU - Yan Zhang
AU - Xiaonan Liu
AU - Xiaowei Huang
AU - Rongrong Wang
AU - Hong Ji
AU - Yongcai Zhao
PY - 2026
DA - 2026/11/02
JO - Diabetes, Metabolic Syndrome and Obesity
DO - 10.2147/dmso.s628886
UR - https://www.dovepress.com/sglt-2-inhibitors-versus-glp-1-receptor-agonists-for-dementia-and-depr-peer-reviewed-fulltext-article-DMSO
AB - Runzhou Pan,1 Bo Wang,2 Yuzheng Li,1 Huiyun Li,1 Xue Liang,1 Yan Zhang,1 Xiaonan Liu,1 Xiaowei Huang,1 Rongrong Wang,1 Hong Ji,1 Yongcai Zhao11Endocrinology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 2Neurology Department, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Yongcai Zhao, Email [email protected]: The comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on dementia and depression risk in patients with type 2 diabetes mellitus (T2DM) remain unclear. We conducted a meta-analysis to directly compare the incidence of dementia and depression-related outcomes between users of these two drug classes.Methods: A systematic literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception to June 1, 2026. Observational studies reporting quantifiable data on dementia or depression-related events in adults with T2DM were included. Detailed information on study design, age, demographic characteristics, eligibility criteria, outcome definitions, and outcome incidence was extracted. Data were pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses involved sequential exclusion of individual studies. Prespecified subgroup analyses examined effect modifiers including geographic region, study design, age, and follow-up duration. Study quality was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence and methodological rigor of this meta-analysis were evaluated using the AMSTAR 2 checklist.Results: Thirteen observational studies comprising 1,055,315 participants were included. Compared with GLP-1RA users, SGLT-2i users had lower rates of all-cause dementia (OR 0.85, 95% CI 0.77– 0.94; P = 0.001), vascular dementia (OR 0.75, 95% CI 0.71– 0.80; P < 0.001), Alzheimer’s disease (OR 0.76, 95% CI 0.72– 0.79; P < 0.001), and composite depression-related outcomes (OR 0.76, 95% CI 0.67– 0.88; P = 0.001), including suicide/self-harm (OR 0.69, 95% CI 0.60– 0.80; P < 0.001) and depression/anxiety (OR 0.78, 95% CI 0.65– 0.93; P = 0.006). Subgroup analyses revealed more pronounced differences in Asian populations (dementia: OR 0.86, 95% CI 0.75– 0.99; I2 = 0%), European cohorts (depression: OR 0.67, 95% CI 0.54– 0.84; I2 = 83%), and in studies that enrolled younger adults (minimum age 18 years, without an upper age restriction) (dementia: OR 0.79, 95% CI 0.76– 0.81; I2 = 0%; depression: OR 0.67, 95% CI 0.54– 0.84; I2 = 83%).Conclusions: In this meta-analysis of observational studies, SGLT-2i use was associated with lower rates of dementia and depression-related outcomes compared with GLP-1RA use in patients with T2DM. Age and geographic region may influence the observed associations. Future randomized controlled trials and studies reporting outcomes stratified by sex, socioeconomic status, and educational level are warranted.Keywords: sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, depression, dementia, meta-analysis, observational studies
SN - 1178-7007
ER -