{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:15:49Z","timestamp":1791944149556,"version":"4.3.4"},"reference-count":146,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,22]],"date-time":"2020-02-22T00:00:00Z","timestamp":1582329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["16K21370"],"award-info":[{"award-number":["16K21370"]}]},{"name":"Taisho Pharmaceutical","award":["No number assigned"],"award-info":[{"award-number":["No number assigned"]}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","award":["No number assigned"],"award-info":[{"award-number":["No number assigned"]}],"id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R\/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans.<\/jats:p>","DOI":"10.3390\/ijms21041509","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T03:33:43Z","timestamp":1582515223000},"page":"1509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease\u2013A Systematic Review"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-0605","authenticated-orcid":false,"given":"Yusaku","family":"Mori","sequence":"first","affiliation":[{"name":"Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, 142-8555 Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-7571","authenticated-orcid":false,"given":"Takanori","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, 830-0011 Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-0005","authenticated-orcid":false,"given":"Tsutomu","family":"Hirano","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, 142-8555 Tokyo, Japan"},{"name":"Diabetes Center, Ebina General Hospital, Ebina, 243-0433 Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-0823","authenticated-orcid":false,"given":"Sho-ichi","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, 142-8555 Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1008862","article-title":"Emerging Risk Factors Collaboration. 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