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In rats, the DPP8\/9 inhibitor produced alopecia, thrombocytopenia, reticulocytopenia, enlarged spleen, multiorgan histopathological changes, and mortality. In dogs, the DPP8\/9 inhibitor produced gastrointestinal toxicity. The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. The DPP8\/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8\/9. These results suggest that assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents.<\/jats:p>","DOI":"10.2337\/diabetes.54.10.2988","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2988-2994","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":457,"title":["Dipeptidyl Peptidase IV Inhibition for the Treatment of Type 2 Diabetes"],"prefix":"10.2337","volume":"54","author":[{"given":"George R.","family":"Lankas","sequence":"first","affiliation":[{"name":"Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Leiting","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders, Merck Research Laboratories, Rahway, New 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