{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:36:08Z","timestamp":1788471368591,"version":"build-2803163510"},"reference-count":18,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022416","name":"Center for Drug Evaluation and Research","doi-asserted-by":"publisher","award":["Task Order 75F40123F19009"],"award-info":[{"award-number":["Task Order 75F40123F19009"]}],"id":[{"id":"10.13039\/100022416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2026,2,24]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The U.S. Food and Drug Administration (FDA) investigated the potential risk of suicidal ideation and behaviors for glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on learning of post-marketing reports of suicidal ideation and behaviors in patients taking GLP-1 RAs. This study assessed a potential association with intentional self-harm comparing GLP-1 RAs to other antidiabetic products.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>We conducted an active-comparator, new-user cohort study\u2014using FDA\u2019s Sentinel System\u2014with data from October 1, 2015, to September 30, 2023. The study included health plan members \u226518 years old diagnosed with type 2 diabetes, newly initiated GLP-1 RAs (n=1 161 983), sodium-glucose cotransporter-2 inhibitors (SGLT-2is, n=1 081 155), or dipeptidyl peptidase-4 inhibitors (DPP-4is, n=1 396 382), and continuously enrolled in a health plan with medical and drug coverage for \u2265183 days. The main outcome was intentional self-harm. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for intentional self-harm events and used inverse probability of treatment weighting of propensity scores to control for confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The comparator groups had a mean age that was slightly above 60 years and similar percentages of males and females. Adjusted incidence rates of intentional self-harm per 1000 person-years were 1.13 for GLP-1 RAs, 1.22 for SGLT-2is, and 1.37 for DPP-4is. Adjusted HRs indicated no increased risk of intentional self-harm comparing GLP-1 RAs to SGLT-2is (HR 0.93; 95%\u2009CI 0.81 to 1.08) or DPP-4is (HR 0.94; 95%\u2009CI 0.82 to 1.07). Subgroup analyses by comorbid obesity and diabetes, psychiatric history, prior intentional self-harm, age, and sex yielded similar results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The use of GLP-1 RAs did not show increased risk of intentional self-harm compared with SGLT-2is or DPP-4is, which provides some reassurance regarding the safety of GLP-1 RA use in patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjdrc-2025-005840","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:45:14Z","timestamp":1773863114000},"page":"e005840","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Association of GLP-1 receptor agonists with intentional self-harm in patients with type 2 diabetes: a Sentinel Distributed Database study"],"prefix":"10.1136","volume":"14","author":[{"given":"Aida","family":"Kuzucan","sequence":"first","affiliation":[{"name":"Formerly at U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van","family":"Tran","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-0806","authenticated-orcid":false,"given":"Jamal T","family":"Jones","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K","family":"Dutcher","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Her","sequence":"additional","affiliation":[{"name":"Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E","family":"Kempner","sequence":"additional","affiliation":[{"name":"Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-8067","authenticated-orcid":false,"given":"Andrew","family":"Mosholder","sequence":"additional","affiliation":[{"name":"Formerly at U.S. Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Round","sequence":"additional","affiliation":[{"name":"Harvard Pilgrim Health Care Institute LLC, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sengwee","family":"Toh","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer G","family":"Lyons","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026031812450833000_14.2.e005840.1","doi-asserted-by":"crossref","DOI":"10.1155\/2011\/432607","article-title":"Rimonabant: From RIO to Ban","volume":"2011","author":"Sam","year":"2011","journal-title":"J Obes"},{"key":"2026031812450833000_14.2.e005840.2","unstructured":"FDA . Update on fda\u2019s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. 2024. Available: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type"},{"key":"2026031812450833000_14.2.e005840.3","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.320"},{"key":"2026031812450833000_14.2.e005840.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1809643"},{"key":"2026031812450833000_14.2.e005840.5","first-page":"1","article-title":"Issues in Developing a Surveillance Case Definition for Nonfatal Suicide Attempt and Intentional Self-harm Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Coded Data","volume":"2018","author":"Hedegaard","year":"2018","journal-title":"Natl Health Stat Report"},{"key":"2026031812450833000_14.2.e005840.6","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1093\/jamia\/ocac144","article-title":"Accuracy of ICD-10-CM encounter diagnoses from health records for identifying self-harm events","volume":"29","author":"Simon","year":"2022","journal-title":"J Am Med Inform Assoc"},{"key":"2026031812450833000_14.2.e005840.7","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12197"},{"key":"2026031812450833000_14.2.e005840.8","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/00001648-200009000-00011","article-title":"Marginal Structural Models and Causal Inference in Epidemiology","volume":"11","author":"Robins","year":"2000","journal-title":"Epidemiology (Sunnyvale)"},{"key":"2026031812450833000_14.2.e005840.9","doi-asserted-by":"publisher","DOI":"10.1080\/00273171.2011.568786"},{"key":"2026031812450833000_14.2.e005840.10","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1177\/0962280219869742","article-title":"Inverse probability weighted Cox model in multi-site studies without sharing individual-level data","volume":"29","author":"Shu","year":"2020","journal-title":"Stat Methods Med Res"},{"key":"2026031812450833000_14.2.e005840.11","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp173"},{"key":"2026031812450833000_14.2.e005840.12","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/69.1.239"},{"key":"2026031812450833000_14.2.e005840.13","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291715001804"},{"key":"2026031812450833000_14.2.e005840.14","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-023830","article-title":"Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink","volume":"8","author":"Gamble","year":"2018","journal-title":"BMJ Open"},{"key":"2026031812450833000_14.2.e005840.15","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-080679","article-title":"Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study","volume":"388","author":"Shapiro","year":"2025","journal-title":"BMJ"},{"key":"2026031812450833000_14.2.e005840.16","doi-asserted-by":"publisher","DOI":"10.7326\/M24-0329"},{"key":"2026031812450833000_14.2.e005840.17","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41591-023-02672-2","article-title":"Association of semaglutide with risk of suicidal ideation in a real-world cohort","volume":"30","author":"Wang","year":"2024","journal-title":"Nat Med"},{"key":"2026031812450833000_14.2.e005840.18","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1001\/jamainternmed.2024.4369","article-title":"GLP-1 Receptor Agonist Use and Risk of Suicide Death","volume":"184","author":"Ueda","year":"2024","journal-title":"JAMA Intern Med"}],"container-title":["BMJ Open Diabetes Research &amp; Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjdrc-2025-005840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:45:16Z","timestamp":1773863116000},"score":1,"resource":{"primary":{"URL":"https:\/\/drc.bmj.com\/lookup\/doi\/10.1136\/bmjdrc-2025-005840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":18,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,3,18]]},"published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1136\/bmjdrc-2025-005840"],"URL":"https:\/\/doi.org\/10.1136\/bmjdrc-2025-005840","relation":{},"ISSN":["2052-4897"],"issn-type":[{"value":"2052-4897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]}}}