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In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP\/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Using single-nuclei RNA sequencing, we identified the cellular phenotypes of AP\/NTS cells expressing GIPR and GLP-1R on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in \u03b3-aminobutyric acid-ergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.<\/jats:p>","DOI":"10.2337\/db21-0459","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T11:05:15Z","timestamp":1628679915000},"page":"2545-2553","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":197,"title":["GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist\u2013Induced Nausea and Emesis in Preclinical Models"],"prefix":"10.2337","volume":"70","author":[{"given":"Tito","family":"Borner","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Pennsylvania, Philadelphia, PA"},{"name":"Department of Biobehavioral Health Sciences, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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