{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:43:16Z","timestamp":1790602996441,"version":"4.1.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 17\u202f288 patients (mean [SD] age, 70.7 [12.0] years; 10\u202f010 male [57.9%]), 1583 initiated GLP-1 RAs and 15\u202f705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.55952","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:31:21Z","timestamp":1769617881000},"page":"e2555952","source":"Crossref","is-referenced-by-count":6,"title":["Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes"],"prefix":"10.1001","volume":"9","author":[{"given":"Fu-Chih","family":"Hsiao","sequence":"first","affiliation":[{"name":"The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzyy-Jer","family":"Hsu","sequence":"additional","affiliation":[{"name":"The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 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