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We aimed to compare rates of severe motility\u2010related gastrointestinal adverse events between initiators of GLP\u20101 based therapies versus sodium\u2010glucose co\u2010transporter 2 inhibitors (SGLT\u20102i).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      This new\u2010user active\n                      <jats:bold>\u2010<\/jats:bold>\n                      comparative cohort study used two de\u2010identified US commercial healthcare databases to identify adults with type\u20102 diabetes without a prior history of major gastrointestinal conditions who initiated GLP\u20101 based therapies (GLP\u20101 receptor agonists or tirzepatide) or SGLT\u20102i. The main outcome was a composite of severe constipation, gastroparesis, and gastrointestinal obstruction. We estimated incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) after propensity score matching.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 313\u2009342 matched pairs of GLP\u20101 based therapies and SGLT\u20102i initiators (mean age 60\u2009years; 45% female), followed on treatment for a median of 5.2\u2009months, incidence rates of the composite outcome were 1.02 among GLP\u20101 based therapies versus 0.75 among SGLT\u20102i initiators per 100 person\u2010years. The risk was higher among GLP\u20101 based therapies versus SGLT\u20102i initiators (rate difference 0.27 per 100 person\u2010years; HR 1.37, 95% CI 1.30, 1.45) for the composite event and each individual component. This relative increased risk was consistent across subgroups stratified by GLP\u20101 based therapies agent, age, sex, BMI, frailty level, diabetes severity, or opioid use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The absolute risk of motility\u2010related gastrointestinal adverse events was 1% or less but was higher among initiators of GLP\u20101 based therapies compared to SGLT\u20102i. These findings can inform the risk benefit assessment by clinicians before initiating these treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70963","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:00:42Z","timestamp":1780635642000},"page":"7494-7504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glucagon\u2010Like Peptide\u20101 Based Therapies and the Risk of Severe Gastrointestinal Motility Adverse Events: A Cohort Study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-0442","authenticated-orcid":false,"given":"Wajd","family":"Alkabbani","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Ontario Canada"},{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Crisafulli","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Diagnostics and Public Health University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Paik","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of Renal (Kidney) Medicine, Department of Medicine Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"New England Geriatric Research Education and Clinical Center VA Boston Healthcare System  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7430-1848","authenticated-orcid":false,"given":"Ali","family":"Tavakkoli","sequence":"additional","affiliation":[{"name":"Division of General and GI Surgery Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsiaryna","family":"Bykov","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Glynn","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Wexler","sequence":"additional","affiliation":[{"name":"Diabetes Unit Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8809-9898","authenticated-orcid":false,"given":"Elisabetta","family":"Patorno","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Division of General Internal Medicine &amp; 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