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People with obesity initiating semaglutide were matched 1:1 via propensity score matching (215 covariates) to those initiating active comparators or usual care. The with\u2010T2D cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919\u2009824\u201393\u2009519 matched pairs per comparison) was followed for 3\u2009years; the without\u2010T2D cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910\u2009323\u201356\u2009225 pairs) for 2\u2009years. The primary outcome was major osteoporotic fracture (MOF). Secondary outcomes included osteoporosis diagnosis; exploratory outcomes included osteoarthritis and gout.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the with\u2010T2D cohort, semaglutide initiation was associated with a lower risk of MOF compared with empagliflozin (HR 0.69; 95% CI 0.61\u20130.77), glipizide (HR 0.72; 0.63\u20130.83) and usual care (HR 0.84; 0.76\u20130.93). In the without\u2010T2D cohort, no significant associations with MOF were observed across any comparison (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). Osteoporosis risk did not differ significantly in most comparisons in either cohort. Exploratory analyses of osteoarthritis and gout showed inconsistent patterns across comparators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among people with obesity and T2D, semaglutide initiation was associated with a lower risk of MOF over 3\u2009years compared with other glucose\u2010lowering agents and usual care. This association was not observed in people with obesity without T2D. These findings support further investigation of the skeletal effects of GLP\u20101 receptor agonists.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70786","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:26:11Z","timestamp":1776741971000},"page":"5834-5847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Associations of Semaglutide With Skeletal Outcomes in People With Obesity, With and Without Type 2 Diabetes: A Target Trial Emulation"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-1685","authenticated-orcid":false,"given":"Yu\u2010Nan","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Genetics and Endocrinology, Department of Pediatrics Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Yu","family":"Tsou","sequence":"additional","affiliation":[{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin\u2010Hung","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Genetics and Endocrinology, Department of Pediatrics Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u2010Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Genetics and Endocrinology, Department of Pediatrics Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao\u2010Chia","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Genetics and Endocrinology, Department of Pediatrics Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2637-6185","authenticated-orcid":false,"given":"Hao\u2010I","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Taiwan University  Taipei Taiwan"},{"name":"Department of Education National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Meyerowitz\u2010Katz","sequence":"additional","affiliation":[{"name":"School of Health and Society, University of Wollongong  Wollongong Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Biology and Precision Therapeutics Center, China Medical University  Taichung Taiwan"},{"name":"Master Program for Biomedical Engineering China Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pen\u2010Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Genetics and Endocrinology, Department of Pediatrics Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02750-2"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0572"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00283-1"},{"issue":"5","key":"e_1_2_13_6_1","first-page":"S59","article-title":"Obesity and Weight Loss in the Treatment and Prevention of Osteoarthritis","volume":"4","author":"Vincent H. 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