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To investigate the association between diabetes medication use and frailty, we conducted an observational cohort analysis of older adults with diabetes enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Diabetes at baseline (<jats:italic>N<\/jats:italic>\u2009=\u20092045) was defined as self-reported diabetes, fasting blood glucose levels\u2009&gt;\u2009125\u00a0mg\/dL, or use of diabetes medication. Diabetes medication exposure at baseline was categorized as use of metformin only (monotherapy) (<jats:italic>N<\/jats:italic>\u2009=\u2009545), metformin combined with other diabetes medications (<jats:italic>N<\/jats:italic>\u2009=\u2009420), other diabetes medications only (<jats:italic>N<\/jats:italic>\u2009=\u2009200), or no diabetes medications (<jats:italic>N<\/jats:italic>\u2009=\u2009880). Frailty was defined using a modified Fried frailty phenotype (presence of\u2009\u2265\u20093 of 5 criteria) and a deficit accumulation frailty index (FI,\u00a0score\u2009&gt;\u20090.21\/1.00). Mixed effects ordinal logistic regression models revealed the odds of frailty at baseline were highest for the other diabetes medications only group, but this difference remained consistent over follow-up. After adjustment for covariates, including baseline pre-frailty, no differences in the rates of Fried or FI frailty were observed among the diabetes medication exposure groups. These findings suggest that diabetes medication exposure in older adults with diabetes does not directly impact frailty risk.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s11357-025-01598-6","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T21:53:09Z","timestamp":1742248389000},"page":"5169-5183","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frailty incidence by diabetes treatment regimens in older adults with diabetes mellitus in the ASPirin in Reducing Events in the Elderly Study"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1116-302X","authenticated-orcid":false,"given":"Sara E.","family":"Espinoza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan C.","family":"Broder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory","family":"Wolfe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj C.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne G.","family":"Orchard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn L.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"3","key":"1598_CR1","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2666-7568(20)30014-3","volume":"1","author":"P Hanlon","year":"2020","unstructured":"Hanlon P, Faur\u00e9 I, Corcoran N, et al. 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