{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:04:33Z","timestamp":1793210673175,"version":"4.5.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The head-to-head comparative effectiveness and safety of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) are not well understood.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare risks of kidney, cardiovascular, and death outcomes among patients with type 2 diabetes initiating GLP-1RAs in the Department of Veterans Affairs (VA) health system.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This comparative effectiveness study used an active-comparator, new-user target trial\u2013emulation design with national data linked among the VA, Medicare, and US Renal Data System. Participants were GLP-1RA\u2013naive veterans with type 2 diabetes and without end-stage kidney disease treated with metformin who started liraglutide, semaglutide, or dulaglutide between January 1, 2018, and December 31, 2021. Data were analyzed from September 2024 to June 2025.<\/jats:p><\/jats:sec>Exposure<\/jats:title>Liraglutide, semaglutide, or dulaglutide.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Kidney failure (sustained estimated glomerular filtration rate &amp;lt;15 mL\/min\/1.73 m2<\/jats:sup> or initiation of kidney replacement therapy), composite cardiovascular and kidney metabolic (CKM) events (kidney failure or major adverse cardiovascular events [MACE]; myocardial infarction, heart failure, or stroke\/transient ischemic attack), MACE, all-cause death, and adverse gastrointestinal events (gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis) were evaluated separately through March 31, 2023.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 21\u202f790 included veterans (mean [SD] age, 63.5 [10.8] years, 19\u202f823 [91.0%] male), 5425 (24.9%), 10\u202f838 (49.7%), and 5527 (24.9%) initiated liraglutide, semaglutide, and dulaglutide, respectively. In weighted Cox regression models, compared with initiation of semaglutide, liraglutide initiation had similar hazards for kidney failure (hazard ratio [HR], 0.93; 95% CI, 0.60-1.44), the CKM composite outcome (HR, 0.96; 95% CI, 0.84-1.10), and MACE (HR, 0.95; 95% CI, 0.83-1.09). Results were similar with liraglutide vs dulaglutide and dulaglutide vs semaglutide comparisons. Liraglutide had significantly lower hazard of all-cause death compared with semaglutide under intent-to-treat analyses (HR, 0.83; 95% CI, 0.69-0.99), which lost significance in per-protocol models. Compared with dulaglutide, liraglutide was associated with a lower risk of all-cause mortality in both the intent-to-treat (HR, 0.69; 95% CI, 0.58-0.83) and per-protocol (HR, 0.50; 95% CI, 0.31-0.82) analyses, but compared with semaglutide, dulaglutide had higher hazard of mortality only in the per-protocol model (HR, 1.72; 95% CI, 1.20-2.47). The only observed difference for the gastrointestinal adverse events was a decreased risk for gallstones and acute cholecystitis with dulaglutide vs semaglutide (gallstones: HR, 0.72; 95% CI, 0.54-0.95; acute cholecystitis: HR, 0.62; 95% CI, 0.39-0.99).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this comparative effectiveness study in veterans with diabetes, liraglutide, semaglutide, and dulaglutide initiators had similar risks for kidney and cardiovascular outcomes. Head-to-head randomized trials are needed to confirm these findings.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.37297","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:02:04Z","timestamp":1760367724000},"page":"e2537297","source":"Crossref","is-referenced-by-count":11,"title":["Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes"],"prefix":"10.1001","volume":"8","author":[{"given":"Catherine G.","family":"Derington","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora"},{"name":"Adult & Child Center for Outcomes Research & Delivery Science, University of Colorado Anschutz Medical Campus, Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Sarwal","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of 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