{"doi":"10.1111/dom.70384","title":"Association between glucagon‐like peptide‐1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation","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.","journal":"Diabetes Obesity and Metabolism","year":2025,"id":549673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8664,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":545934,"name":"Huilin Tang","orcid":"0000-0002-5814-6657","position":1,"is_corresponding":false},{"id":1163291,"name":"Bingyu Zhang","orcid":"0000-0001-7176-249X","position":2,"is_corresponding":false},{"id":27175,"name":"D. F. Zhang","orcid":"0000-0001-7335-4983","position":3,"is_corresponding":false},{"id":1375867,"name":"Yiwen Lu","orcid":"0009-0000-9591-2261","position":4,"is_corresponding":false},{"id":118178,"name":"Lu Li","orcid":null,"position":5,"is_corresponding":false},{"id":1163292,"name":"Jiajie Chen","orcid":"0009-0008-7402-6883","position":6,"is_corresponding":false},{"id":235491,"name":"Yong Chen","orcid":"0009-0001-0019-6889","position":7,"is_corresponding":false},{"id":1256172,"name":"David A Asch","orcid":null,"position":9,"is_corresponding":false},{"id":145735,"name":"Ting Zhou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41424236","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}