{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:40:37Z","timestamp":1792726837970,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Across the full spectrum of major clinical trials evaluating glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101 RAs) for obesity management, nausea consistently emerges as the most documented adverse effect, yet the methods used to capture it have received little scrutiny relative to their clinical importance. This narrative review traces how nausea was actually measured across the pivotal liraglutide (SCALE), semaglutide (STEP) and tirzepatide (SURMOUNT) obesity trial programmes, and situates those methods against the standards set out in the Consensus\u2010based Standards for the selection of health Measurement Instruments (COSMIN) and the United States Food and Drug Administration's Patient\u2010Focused Drug Development guidance. Across all three drug classes, nausea was ascertained through investigator\u2010recorded, spontaneously reported adverse events coded to the Medical Dictionary for Regulatory Activities (MedDRA), a pharmacovigilance framework built for a different purpose than symptom characterization, rather than through any validated, symptom\u2010specific patient\u2010reported outcome instrument. This observation gains further importance when considered alongside a second, less widely recognized fact: these same trial programmes devoted substantial methodological effort to developing and implementing a rigorous, quality of life measure specifically for obesity, the Impact of Weight on Quality of Life\u2010Lite Clinical Trials Version in addition to the Short Form\u201036 and EuroQol\u20105D. We argue that this asymmetry, more than any single mismeasurement, helps explain why real\u2010world persistence with these agents falls so far short of what trial\u2010reported tolerability figures would predict, and we outline what a fit\u2010for\u2010purpose metabolic nausea instrument would need to capture that adverse\u2010event surveillance cannot.<\/jats:p>","DOI":"10.1111\/dom.71474","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:24:22Z","timestamp":1792725862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How Well Are We Measuring Nausea? A Narrative Review of Patient\u2010Reported Outcome Gaps in\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonist Obesity Trials"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8987-3997","authenticated-orcid":false,"given":"Lima","family":"Oria","sequence":"first","affiliation":[{"name":"International School of Medicine, Istanbul Medipol University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2359-4959","authenticated-orcid":false,"given":"Mohammad","family":"Darkhabani","sequence":"additional","affiliation":[{"name":"International School of Medicine, Istanbul Medipol University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1411892","article-title":"A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management","volume":"373","author":"Pi\u2010Sunyer X.","year":"2015","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide Once Weekly for the Treatment of Obesity","volume":"387","author":"Jastreboff A. M.","year":"2022","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/dom.12824","article-title":"Occurrence of Nausea, Vomiting and Diarrhoea Reported as Adverse Events in Clinical Trials Studying Glucagon\u2010Like Peptide\u20101 Receptor Agonists: A Systematic Analysis of Published Clinical Trials","volume":"19","author":"Bettge K.","year":"2017","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24331"},{"key":"e_1_2_14_6_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s11136-018-1829-0","article-title":"COSMIN Methodology for Evaluating the Content Validity of Patient\u2010Reported Outcome Measures: A Delphi Study","volume":"27","author":"Terwee C. B.","year":"2018","journal-title":"Quality of Life Research"},{"key":"e_1_2_14_7_1","volume-title":"Patient\u2010Focused Drug Development Guidance 3: Select, Develop or Modify Fit\u2010For\u2010Purpose Clinical Outcome Assessments","author":"U.S. Food and Drug Administration","year":"2022"},{"key":"e_1_2_14_8_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page M. J.","year":"2021","journal-title":"BMJ"},{"key":"e_1_2_14_9_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1001\/jama.2015.9676","article-title":"Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial","volume":"314","author":"Davies M. J.","year":"2015","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_14_10_1","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once\u2010Weekly Semaglutide in Adults With Overweight or Obesity","volume":"384","author":"Wilding J. P. H.","year":"2021","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_14_11_1","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1001\/jama.2021.1831","article-title":"Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial","volume":"325","author":"Wadden T. A.","year":"2021","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_14_12_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1001\/jama.2021.3224","article-title":"Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial","volume":"325","author":"Rubino D.","year":"2021","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_14_13_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/dom.14551","article-title":"Gastrointestinal Tolerability of Once\u2010Weekly Semaglutide 2.4 mg in Adults With Overweight or Obesity, and the Relationship Between Gastrointestinal Adverse Events and Weight Loss","volume":"24","author":"Wharton S.","year":"2022","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"e_1_2_14_14_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(23)01200-X","article-title":"Tirzepatide Once Weekly for the Treatment of Obesity in People With Type 2 Diabetes (SURMOUNT\u20102): A Double\u2010Blind, Randomised, Multicentre, Placebo\u2010Controlled, Phase 3 Trial","volume":"402","author":"Garvey W. T.","year":"2023","journal-title":"Lancet"},{"key":"e_1_2_14_15_1","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1038\/s41591-023-02597-w","article-title":"Tirzepatide After Intensive Lifestyle Intervention in Adults With Overweight or Obesity: The SURMOUNT\u20103 Phase 3 Trial","volume":"29","author":"Wadden T. A.","year":"2023","journal-title":"Nature Medicine"},{"key":"e_1_2_14_16_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1001\/jama.2023.24945","article-title":"Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT\u20104 Randomized Clinical Trial","volume":"331","author":"Aronne L. J.","year":"2024","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16176"},{"issue":"11","key":"e_1_2_14_18_1","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.7326\/M23-2019","article-title":"Accurate Measurements of Gastric Emptying and Gastrointestinal Symptoms in the Evaluation of Glucagon\u2010Like Peptide\u20101 Receptor Agonists","volume":"176","author":"Jalleh R. J.","year":"2023","journal-title":"Annals of Internal Medicine"},{"issue":"4","key":"e_1_2_14_19_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI194740","article-title":"The Science of Safety: Adverse Effects of GLP\u20101 Receptor Agonists as Glucose\u2010Lowering and Obesity Medications","volume":"136","author":"Jalleh R. J.","year":"2026","journal-title":"Journal of Clinical Investigation"},{"issue":"4","key":"e_1_2_14_20_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1365-2982.2004.00530.x","article-title":"Association of Upper and Lower Gastrointestinal Tract Symptoms With Body Mass Index in an Australian Cohort","volume":"16","author":"Talley N. J.","year":"2004","journal-title":"Neurogastroenterology and Motility"},{"issue":"16","key":"e_1_2_14_21_1","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1001\/archinte.161.16.1989","article-title":"Prevalence of Gastrointestinal Symptoms Associated With Diabetes Mellitus: A Population\u2010Based Survey of 15,000 Adults","volume":"161","author":"Bytzer P.","year":"2001","journal-title":"Archives of Internal Medicine"},{"issue":"3","key":"e_1_2_14_22_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.2337\/dc17-1536","article-title":"Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management","volume":"41","author":"Du Y. T.","year":"2018","journal-title":"Diabetes Care"},{"key":"e_1_2_14_23_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/BF00434947","article-title":"Quality of Life Consequences of Chemotherapy\u2010Induced Emesis","volume":"1","author":"Lindley C. M.","year":"1992","journal-title":"Quality of Life Research"},{"key":"e_1_2_14_24_1","first-page":"522","article-title":"Assessing the Impact of Chemotherapy\u2010Induced Nausea and Vomiting on Patients' Daily Lives: A Modified Version of the Functional Living Index\u2010Emesis (FLIE) With 5\u2010Day Recall","volume":"11","author":"Martin A. R.","year":"2003","journal-title":"Supportive Care in Cancer"},{"issue":"1","key":"e_1_2_14_25_1","first-page":"1","article-title":"Clinical Consequences of Delayed Gastric Emptying With GLP\u20101 Receptor Agonists and Tirzepatide","volume":"110","author":"Jalleh R. J.","year":"2025","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"issue":"10","key":"e_1_2_14_26_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S2468-1253(24)00188-2","article-title":"Gastrointestinal Effects of GLP\u20101 Receptor Agonists: Mechanisms, Management, and Future Directions","volume":"9","author":"Jalleh R. J.","year":"2024","journal-title":"Lancet Gastroenterology & Hepatology"},{"issue":"7","key":"e_1_2_14_27_1","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.3390\/nu12071962","article-title":"Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients With Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution","volume":"12","author":"Jalleh R.","year":"2020","journal-title":"Nutrients"},{"issue":"4","key":"e_1_2_14_28_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1023\/B:QURE.0000021689.86296.e4","article-title":"Gastroparesis Cardinal Symptom Index (GCSI): Development and Validation of a Patient Reported Assessment of Severity of Gastroparesis Symptoms","volume":"13","author":"Revicki D. A.","year":"2004","journal-title":"Quality of Life Research"},{"issue":"10","key":"e_1_2_14_29_1","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s11136-004-9567-x","article-title":"Development and Psychometric Evaluation of the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI\u2010SYM) in Patients With Upper Gastrointestinal Disorders","volume":"13","author":"Rentz A. M.","year":"2004","journal-title":"Quality of Life Research"},{"issue":"2","key":"e_1_2_14_30_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/BF01535722","article-title":"GSRS\u2014A Clinical Rating Scale for Gastrointestinal Symptoms in Patients With Irritable Bowel Syndrome and Peptic Ulcer Disease","volume":"33","author":"Svedlund J.","year":"1988","journal-title":"Digestive Diseases and Sciences"},{"issue":"7","key":"e_1_2_14_31_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/j.1463-1326.2008.00861.x","article-title":"Patient\u2010Reported Rating of Gastrointestinal Adverse Effects During Treatment of Type 2 Diabetes With the Once\u2010Daily Human GLP\u20101 Analogue, Liraglutide","volume":"10","author":"Horowitz M.","year":"2008","journal-title":"Diabetes, Obesity & Metabolism"},{"issue":"6","key":"e_1_2_14_32_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3390\/biom15060796","article-title":"Retatrutide\u2014A Game Changer in Obesity Pharmacotherapy","volume":"15","author":"Katsi V.","year":"2025","journal-title":"Biomolecules"},{"issue":"6","key":"e_1_2_14_33_1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa2301972","article-title":"Triple\u2010Hormone\u2010Receptor Agonist Retatrutide for Obesity\u2014A Phase 2 Trial","volume":"389","author":"Jastreboff A. M.","year":"2023","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_14_34_1","unstructured":"ClinicalTrials.gov [Internet] \u201cA Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight (TRIUMPH\u20101) \u201d Bethesda (MD): National Library of Medicine (US) Identifier NCT05929066."},{"key":"e_1_2_14_35_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/cob.12197","article-title":"Development of a Clinical Trials Version of the Impact of Weight on Quality of Life\u2010Lite Questionnaire (IWQOL\u2010Lite Clinical Trials Version): Results From Two Qualitative Studies","volume":"7","author":"Kolotkin R. L.","year":"2017","journal-title":"Clinical Obesity"},{"key":"e_1_2_14_36_1","doi-asserted-by":"crossref","DOI":"10.1111\/cob.12310","article-title":"Validation of a New Measure of Quality of Life in Obesity Trials: Impact of Weight on Quality of Life\u2010Lite Clinical Trials Version","volume":"9","author":"Kolotkin R. L.","year":"2019","journal-title":"Clinical Obesity"},{"key":"e_1_2_14_37_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/dom.16046","article-title":"Association Between Weight Reduction Achieved With Tirzepatide and Quality of Life in Adults With Obesity: Results From the SURMOUNT\u20101 Study","volume":"27","author":"Gudzune K. A.","year":"2025","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"e_1_2_14_38_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s41687-025-00841-0","article-title":"The Evaluation of Clinical Outcomes Assessments and Digital Health Technologies in Clinical Trials for Obesity","volume":"9","author":"Goetz I. A.","year":"2025","journal-title":"Journal of Patient\u2010Reported Outcomes"},{"key":"e_1_2_14_39_1","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.2147\/PPA.S277676","article-title":"Real\u2010World Adherence and Discontinuation of Glucagon\u2010Like Peptide\u20101 Receptor Agonists Therapy in Type 2 Diabetes Mellitus Patients in the United States","volume":"14","author":"Weiss T.","year":"2020","journal-title":"Patient Preference and Adherence"},{"issue":"12","key":"e_1_2_14_40_1","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1002\/oby.70058","article-title":"Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice","volume":"33","author":"Gasoyan H.","year":"2025","journal-title":"Obesity (Silver Spring)"},{"key":"e_1_2_14_41_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/s13063-016-1555-2","article-title":"How to Select Outcome Measurement Instruments for Outcomes Included in a Core Outcome Set\u2014A Practical Guideline","volume":"17","author":"Prinsen C. A. C.","year":"2016","journal-title":"Trials"},{"key":"e_1_2_14_42_1","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.jval.2011.06.014","article-title":"Content Validity\u2014Establishing and Reporting the Evidence in Newly Developed Patient\u2010Reported Outcome Instruments for Medical Product Evaluation: ISPOR PRO Good Research Practices Task Force Report: Part 1\u2014Eliciting Concepts for a New PRO Instrument","volume":"14","author":"Patrick D. L.","year":"2011","journal-title":"Value in Health"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71474","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.71474","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:24:31Z","timestamp":1792725871000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.71474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":41,"alternative-id":["10.1111\/dom.71474"],"URL":"https:\/\/doi.org\/10.1111\/dom.71474","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2026-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"dom.71474"}}