{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:20:51Z","timestamp":1787552451333,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) and dual GLP\u20101\/GIP receptor agonists have transformed the pharmacological management of type 2 diabetes (T2D) and obesity, yet substantial interindividual variability in treatment response remains a defining clinical challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Narrative review. PubMed was searched to 25 May 2026 (English language, human studies, 2005\u20132026) for biological, genetic, metabolic, hormonal, behavioural and psychosocial predictors of differential response. Evidence is organised across three clinically distinct contexts: glycaemic control in T2D; weight loss in people with overweight or obesity without T2D; and dual metabolic benefit in those with both conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Response heterogeneity is most pronounced in obesity without diabetes, where non\u2010response\u2014commonly defined as less than 5% total body weight loss\u2014affects approximately 10% of participants in controlled trials, with real\u2010world cohorts suggesting a higher frequency in routine practice; glycaemic non\u2010response in T2D is less common but clinically significant. Across all three contexts, early on\u2010treatment response is the most readily actionable predictor currently available. A recent large genome\u2010wide association study reported associations between variation in the GLP1R drug\u2010target gene and both weight\u2010loss efficacy and gastrointestinal tolerability, and between agent\u2010specific GIPR variants and nausea and vomiting with tirzepatide; these self\u2010reported, single\u2010cohort and as\u2010yet unreplicated findings remain hypothesis\u2010generating rather than a basis for individual\u2010level genotyping. Metabolic, microbiome and neuroendocrine predictors are at a comparably preliminary stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>No single baseline characteristic reliably predicts response. Structured assessment of early on\u2010treatment response is currently the most defensible basis for individualising therapy; genetic, metabolic and microbiome markers require prospective replication before clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71226","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:50:10Z","timestamp":1787550610000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Responders Vs. Non\u2010Responders or How to Predict the Response to\n                    <scp>GLP<\/scp>\n                    \u20101 or\n                    <scp>GLP<\/scp>\n                    \u20101\/\n                    <scp>GIP<\/scp>\n                    Receptor Agonist Therapy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-4927","authenticated-orcid":false,"given":"Alina","family":"Kury\u0142owicz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Geriatric Cardiology Center of Postgraduate Medical Education  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2396-8885","authenticated-orcid":false,"given":"Leszek","family":"Czupryniak","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Internal Medicine Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"issue":"11","key":"e_1_2_16_2_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. 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