{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:56Z","timestamp":1792471136337,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine the effect of second\u2010line treatments (insulin secretagogues, thiazolidinediones, glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonists, dipeptidyl peptidase\u20104 (DPP\u20104) inhibitors or sodium\u2010glucose co\u2010transporter 2 (SGLT\u20102) inhibitors) on time to insulin initiation among patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research Design and Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using the Clinical Practice Research Datalink (CPRD) Aurum. Initiation of metformin monotherapy (1998\u20132021) defined base cohort entry, and initiation of second\u2010line treatment (2013\u20132021) defined study cohort entry (time zero). After propensity score trimming, we applied inverse probability of treatment weighted Cox models to estimate the association between second\u2010line agents and time to insulin initiation. The secondary outcome was time to treatment modification, defined as the addition of or switch to another antidiabetic drug class.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analytic cohort included 64\u2009404 patients; 44% initiated DPP\u20104 inhibitors, 36% insulin secretagogues, 18% SGLT\u20102 inhibitors, 1% thiazolidinediones and 3% GLP\u20101 receptor agonists. Over a mean follow\u2010up of 2.9\u2009years, initiation of TZDs, DPP\u20104 inhibitors, or SGLT\u20102 inhibitors was associated with a lower risk of insulin initiation than initiation of insulin secretagogues (HR [95% CI]: 0.59 [0.43\u20130.83], 0.75 [0.69\u20130.80] and 0.62 [0.56\u20130.68], respectively). For treatment modification, the risk was higher among TZD and DPP\u20104 inhibitor initiators, and slightly lower among SGLT\u20102 inhibitor initiators and GLP\u20101 receptor agonist initiators than among insulin secretagogue initiators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides real\u2010world evidence that TZDs, DPP\u20104 inhibitors and SGLT\u20102 inhibitors may offer an advantage over insulin secretagogues in delaying insulin initiation after metformin monotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71182","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:13:38Z","timestamp":1786079618000},"page":"9655-9667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time to Insulin Initiation Among Patients With Type 2 Diabetes Treated With Second\u2010Line Antidiabetic Drugs"],"prefix":"10.1111","volume":"28","author":[{"given":"Ya\u2010Hui","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Rollin School of Public Health Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Centre for Clinical Epidemiology Lady Davis Institute, Jewish General Hospital  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Zapata\u2010Bravo","sequence":"additional","affiliation":[{"name":"Centre for Clinical Epidemiology Lady Davis Institute, Jewish General Hospital  Montreal Quebec Canada"},{"name":"Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Platt","sequence":"additional","affiliation":[{"name":"Centre for Clinical Epidemiology Lady Davis Institute, Jewish General Hospital  Montreal Quebec Canada"},{"name":"Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health McGill University  Montreal Quebec Canada"},{"name":"Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Reynier","sequence":"additional","affiliation":[{"name":"Centre for Clinical Epidemiology Lady Davis Institute, Jewish General Hospital  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana H. 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