{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:25:32Z","timestamp":1792765532947,"version":"4.5.0"},"reference-count":134,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To provide a comprehensive overview of the cardiovascular and renal effects of glucose\u2010dependent insulinotropic polypeptide (GIP) by integrating its physiological role with recent human trial data on tirzepatide, the first dual GIP and glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This narrative review synthesizes key physiological data of native GIP across tissues\u2014especially the heart, vessels, kidney, and adipose tissue\u2014and summarizes clinical evidence from the SUMMIT and the SURPASS programmes. Central to this review is the analysis of the SURPASS\u2010CVOT trial, which compared the cardiovascular protective effects of tirzepatide versus dulaglutide in individuals with type 2 diabetes and established atherosclerotic CV disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Preclinical data regarding GIP receptor modulation in the cardiorenal district remains controversial, a contention partially reflected in recent clinical evidence. Within the innovative framework of SURPASS\u2010CVOT, tirzepatide established non\u2010inferiority to dulaglutide for 3\u2010point MACE while slowing eGFR decline in participants with high\u2010risk chronic kidney disease. Furthermore, the SUMMIT trial demonstrated that in individuals with obesity and heart failure (HF) with preserved ejection fraction, tirzepatide reduced the composite endpoint of CV death or worsening HF events, regardless of baseline kidney function. Despite these advancements, knowledge gaps persist regarding the potential synergistic cardiorenal benefits of combining dual incretin agonism with sodium\u2010glucose cotransporter\u20102 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>While adding GIP receptor agonism to GLP\u20101 receptor agonism clearly improves cardiometabolic risk factors, its precise and independent contribution to long\u2010term CV and renal protection remains to be fully elucidated. Ongoing outcome trials, such as SURMOUNT\u2010MMO and TREASURE\u2010CKD, will provide additional insights into these effects. Furthermore, emerging strategies\u2014including combining GIP receptor antagonism with GLP\u20101 receptor agonism or moving toward triple agonism\u2014represent promising alternatives to favorably modify the multiple determinants of cardiometabolic risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70888","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T01:45:21Z","timestamp":1780019121000},"page":"6509-6532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>GIP<\/scp>\n                    in Cardiovascular and Kidney Disease: From Physiology to Pharmacology"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-5991","authenticated-orcid":false,"given":"Michelantonio","family":"De Fano","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery Perugia University Medical School  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line L.","family":"Haurum","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine R.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Porcellati","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery Perugia University Medical School  Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8190-5140","authenticated-orcid":false,"given":"Andreas","family":"Andersen","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc26-S010"},{"issue":"377","key":"e_1_2_18_3_1","first-page":"13","article-title":"Obesity Collaborators. 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