{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:21Z","timestamp":1791561021464,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":242,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Semaglutide and tirzepatide are typically evaluated through dose escalation, yet many patients in routine care do not reach a recommended maintenance dose due to tolerability, access, cost, supply, or individualized goals. Here, we used repeated 0.25 mg only semaglutide and 2.5 mg only tirzepatide prescription records as real-world proxies for sustained treatment at the lowest approved dose, a prescribing pattern that may overlap with, but does not establish, intentional microdosing. We analyzed de-identified electronic health records (EHRs) from a federated system of 29 million patients. Among 490\u00a0072 semaglutide-treated patients, 814 met the stringent sustained low-dose criterion of at least three distinct 0.25-mg prescriptions spanning at least 6\u2009months from the first to the last qualifying prescription and among 322\u00a0442 tirzepatide-treated patients, 1016 met the analogous criterion of at least three distinct 2.5-mg prescriptions spanning at least 6\u2009months. In a matched head-to-head comparison aided by AI-enabled curation of clinical notes, sustained low-dose tirzepatide showed higher 24-month adverse event rates (P\u2009&amp;lt;\u2009.05) than sustained low-dose semaglutide for constipation (32.6% vs. 22.4%), acute kidney injury (2.7% vs. 0.4%), muscle cramps (8.3% vs. 4%), lumbar disc disease (3.3% vs. 0.3%), dyspnea on exertion (9.6% vs. 6.8%), lentigo (4.7% vs. 0.8%), and actinic keratosis (3.3% vs. 0.6%), whereas sustained low-dose semaglutide (vs. tirzepatide) had higher rates of including otitis (5.6% vs. 2.1%), diaphoresis (5.5% vs. 3.2%), and ankle swelling (6.9% vs. 3.7%). Sustained low-dose tirzepatide was associated with greater weight loss than semaglutide (mean 12-month percent weight change \u22125.5% vs. \u22122.2%; P\u2009&amp;lt;\u2009.05 at all timepoints). Analyses of prescription patterns supported the findings from clinical notes. For example, renal-supportive and hyperkalemia therapies increased after low-dose tirzepatide (5.6% to 9.5% at 12\u2009months, P\u2009=\u2009.016) but not after low-dose semaglutide (8.2% to 6.6%, P\u2009=\u2009.382). Taken together, these observational associations motivate prospective studies to better characterize the outcomes and pharmacology of sustained initiation-dose semaglutide or tirzepatide, and related microdosing studies.<\/jats:p>","DOI":"10.1093\/biomethods\/bpag048","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:10:50Z","timestamp":1788185450000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparison of cardiometabolic benefits and tolerability in patients on sustained low doses of semaglutide or tirzepatide"],"prefix":"10.1093","volume":"11","author":[{"given":"Karthik","family":"Murugadoss","sequence":"first","affiliation":[{"name":"nference Inc. , Cambridge, MA 02142,","place":["United States"]},{"name":"Metabolism Agentic Intelligence Atlas (MAIA) , Cambridge, MA 02142,","place":["United 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