{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:33:34Z","timestamp":1789648414588,"version":"4.0.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long\u2010term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all\u2010cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331\u2009375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n\u2009=\u200945\u2009854) or bisphosphonates (control, n\u2009=\u2009285\u2009521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45\u2009851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long\u2010term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random\u2010effects meta\u2010analysis. Risk of bias and evidence quality were assessed using Cochrane\u2010endorsed tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5\u2009years (hazard ratio 0.83 [95% confidence interval {CI} 0.78\u20100.88]). Secondary analysis showed significant risk reduction in all\u2010cause mortality (0.79 [0.72\u20100.87]) and foot ulceration (0.67 [0.53\u20100.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta\u2010analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79\u20100.87]) (I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200910.76%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all\u2010cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15708","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T06:05:03Z","timestamp":1718863503000},"page":"3673-3683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all\u2010cause mortality in adults, compared with bisphosphonates: An analysis of real\u2010world, cohort data, with a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E.","family":"Henney","sequence":"first","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Watford General Hospital West Hertfordshire Teaching Hospitals NHS Foundation Trust  Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa J.","family":"Hydes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Anson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizheng Steven","family":"Zhao","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research, Faculty of Biology Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Centre for Biomechanics and Rehabilitation Technologies Staffordshire University  Stoke\u2010on\u2010Trent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Metabolism &amp; Nutrition Research Group Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.023"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254451"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-021-05900-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2021.1989194"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3084"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.54734"},{"key":"e_1_2_9_8_1","article-title":"Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study","volume":"381","author":"Houchen L","year":"2023","journal-title":"BMJ"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1865"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad035"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-2607"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/sja.SJA_543_18"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.04.026"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-022-06616-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4065\/83.9.1032"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2022.100420"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-022-01096-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/20420188231170754"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.05.021"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4930"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-023-06845-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107638"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2021.105241"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa851"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12020185"},{"key":"e_1_2_9_30_1","article-title":"Amp, endocrinology. 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