{"doi":"10.1016/j.diabres.2025.112982","title":"Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease","abstract":"AIMS: To compare the association of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) therapies on lower extremity vascular complications and mortality in PAD. METHODS: We conducted a retrospective cohort study using a nationwide U.S. electronic health records database. Adults with PAD and type 2 diabetes who initiated GLP-1RA, SGLT2i, or DPP4i therapy (May 2013-January 2025) were included. Propensity score matching (1:1) balanced baseline characteristics. Cox models estimated hazard ratios (HR) with 95 % confidence intervals (CI) for major amputation (primary outcome), lower extremity revascularization (LER), and all-cause mortality over 3 years follow-up. Subgroup analyses included symptomatic PAD, prior LER, and drug-level comparisons. RESULTS: GLP-1RAs were associated with lower risks of major amputation (HR 0.79 [95 % CI 0.70-0.90]), LER (HR 0.82 [0.76-0.88]), and mortality (HR 0.71 [0.68-0.73]) compared with SGLT2i (n = 77,393 each). Similar reductions were seen versus DPP-4is (n = 39,907 each); SGLT2is and DPP-4is showed comparable risks (n = 42,924 each). GLP-1RA benefits remained significant in symptomatic PAD (p < 0.05) and were associated with lower mortality in LER patients (p < 0.05). Semaglutide and tirzepatide showed the greatest benefit. CONCLUSION: GLP-1RAs were associated with lower limb complication and mortality risks in PAD, supporting a potential vascular benefit that warrants prospective evaluation.","journal":"Diabetes Research and Clinical Practice","year":2025,"id":514583,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9283,"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":1131683,"name":"Forest Lin","orcid":"0009-0009-4448-678X","position":1,"is_corresponding":false},{"id":1377276,"name":"Ivan Y. Luu","orcid":"0000-0003-0233-2044","position":2,"is_corresponding":false},{"id":290440,"name":"Laura Shin","orcid":null,"position":3,"is_corresponding":false},{"id":781482,"name":"Sukgu M. Han","orcid":"0000-0002-0715-4606","position":4,"is_corresponding":false},{"id":289127,"name":"David G. Armstrong","orcid":"0000-0003-1887-9175","position":5,"is_corresponding":false},{"id":533431,"name":"Tze‐Woei Tan","orcid":"0000-0002-6658-9482","position":6,"is_corresponding":false},{"id":1377275,"name":"Alexander T. Hong","orcid":"0000-0002-8689-6391","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:29.165853Z","pmid":"41177308","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":[]}