{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:08:26Z","timestamp":1791457706991,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"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":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonists and sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors are widely used for the treatment of type 2 diabetes, yet their downstream consequences in routine clinical practice remain incompletely characterized. We compared downstream treatment burden following initiation of GLP\u20101 receptor agonists versus SGLT2 inhibitors among adults with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective, propensity score\u2013matched cohort study using a multi\u2010centre electronic health record network. Adults with type 2 diabetes who newly initiated a GLP\u20101 receptor agonist or an SGLT2 inhibitor between 1 January 2017 and 1 June 2025 were included. After 1:1 matching, approximately 164\u2009000 patients were retained in each treatment group. Outcome\u2010specific baseline\u2010free cohorts with uniform washout periods were constructed, yielding sample sizes of approximately 124\u2009000\u2013164\u2009000 per outcome. Primary outcomes were initiation of seven downstream medication classes. Secondary outcomes included gastrointestinal and nutritional diagnoses and health\u2010care utilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across all seven medication classes, downstream pharmacotherapy initiation occurred more frequently among GLP\u20101 initiators. The largest differences were observed for symptom\u2010driven medications, including antidepressant, an absolute risk difference of 3.38% (95% CI \u22123.61 to \u22123.15) and a hazard ratio (HR) of 0.78 (95% CI 0.76\u20130.80), antiemetic, sedatives\/hypnotics. Proton pump inhibitors, laxatives, histamine\u20102 receptor antagonists and antidiarrheal were also more frequently initiated, though differences were modest. Differences in secondary diagnoses were smaller. Gastroesophageal reflux disease and esophagitis were more common after GLP\u20101 initiation, whereas peptic ulcer disease and endoscopic procedures occurred more frequently among SGLT2 initiators. Nutrient deficiency and unspecified anaemia were more frequent following GLP\u20101 therapy. Overall health\u2010care utilization was similar, except for inpatient acute care, which was more frequent among SGLT2 initiators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiation of GLP\u20101 receptor agonists is associated with a downstream pharmacologic cascade characterized by increased use of symptom\u2010driven medication without corresponding increases in health\u2010care utilization. Medication initiation may provide a more sensitive measure of treatment burden than diagnostic codes or utilization metrics in routine diabetes care. To our knowledge, this study represents the largest multicentre real\u2010world evaluation of downstream pharmacologic cascades following initiation of GLP\u20101 receptor agonists and SGLT2 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70718","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:09:33Z","timestamp":1774937373000},"page":"5163-5173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Downstream Treatment Burden and Health\u2010Care Utilization Following Initiation of\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonists or\n                    <scp>SGLT2<\/scp>\n                    Inhibitors in Type 2 Diabetes"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9540-6403","authenticated-orcid":false,"given":"Yazan","family":"Alhamdan","sequence":"first","affiliation":[{"name":"Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney  Camperdown Australia"},{"name":"Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District  St Leonards Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-2404","authenticated-orcid":false,"given":"Jason C.","family":"Hsu","sequence":"additional","affiliation":[{"name":"International Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University  Taipei Taiwan"},{"name":"Clinical Data Center, Office of Data Science, Taipei Medical University  Taipei Taiwan"},{"name":"Clinical Big Data Research Center, Taipei Medical University Hospital  Taipei Taiwan"},{"name":"Research Center of Data Science on Health Care Industry, College of Management, Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-6837","authenticated-orcid":false,"given":"Christine Y.","family":"Lu","sequence":"additional","affiliation":[{"name":"Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney  Camperdown Australia"},{"name":"Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District  St Leonards Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0034"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31149-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2014.0188"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2025.06.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14551"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12010145"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4082\/kjfm.2018.39.3.137"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000484413"},{"key":"e_1_2_10_20_1","unstructured":"FDA 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