{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:39:36Z","timestamp":1765039176595,"version":"build-2065373602"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,9,9]],"date-time":"2012-09-09T00:00:00Z","timestamp":1347148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The present report summarizes rodent studies with vildagliptin, relevant to predicting pancreatitis or pancreatic cancer in man.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>As part of the regulatory development program for vildagliptin, a rodent toxicity program included two 104\u2010week rodent (mouse and rat) carcinogenicity studies that were conducted according to guidelines assigned in Food and Drug Administration's Draft Guidance for Industry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Vildagliptin exposure in animals was evaluated for its effects on endocrine and exocrine pancreas. Two\u2010year carcinogenicity studies were conducted in rats at oral doses up to 900\u2009mg\/kg (approximately 200 times the human exposure at the maximum recommended dose) and in mice at oral doses up to 1000\u2009mg\/kg (up to 240 times the human exposure at the maximum recommended dose). The results from these studies show the expected preservation and growth of the endocrine \u03b2\u2010cells with no significant findings in the exocrine acinar pancreas. There was no evidence of inflammatory infiltrates characteristic of pancreatitis, no palpable mass detection based on gross examination or any microscopic findings indicative of pancreatic islet cell (endocrine), acinar cell (exocrine) or ductal (exocrine) neoplasia in rat or mouse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Evaluation of vildagliptin in 2\u2010year preclinical carcinogenicity studies in both rats and mice indicates that while vildagliptin results in pharmacological benefits to the endocrine pancreas, this was not associated with any evidence of pancreatitis, pancreatic islet cell, acinar cell or ductal neoplasia. These data predict no increased risk of pancreatic cancer in man.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1463-1326.2012.01678.x","type":"journal-article","created":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T13:51:54Z","timestamp":1344520314000},"page":"72-76","source":"Crossref","is-referenced-by-count":27,"title":["Studies in rodents with the dipeptidyl peptidase\u20104 inhibitor vildagliptin to evaluate possible drug\u2010induced pancreatic histological changes that are predictive of pancreatitis and cancer development in man"],"prefix":"10.1111","volume":"15","author":[{"given":"S. J.","family":"Busch","sequence":"first","affiliation":[{"name":"Novartis Institutes of Biomedical Research  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Novartis Institutes of Biomedical Research  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Sahota","sequence":"additional","affiliation":[{"name":"Novartis Institutes of Biomedical Research  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Novartis Institutes of Biomedical Research  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Kothny","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. E.","family":"Foley","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01414.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.10.062"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2167-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051238"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0058"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.018"},{"key":"e_1_2_7_8_1","unstructured":"Guidance for industry: Statistical aspects of the design analysis and interpretation of chronic rodent carcinogenicity studies of pharmaceuticals Draft guidelines May 2001. Rockville MD: US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)."},{"key":"e_1_2_7_9_1","first-page":"252","article-title":"Recommended tissue list for histopathologic examination in repeat\u2010dose toxicity and carcinogenicity studies: a proposal of the Society of Toxicologic Pathology (STP)","volume":"31","author":"Bregman CL","year":"2003","journal-title":"Toxicol Pathol"},{"key":"e_1_2_7_10_1","first-page":"591","volume-title":"Principles and Methods of Toxicology","author":"Frame SR","year":"2008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1078\/0940-2993-00311"},{"key":"e_1_2_7_12_1","unstructured":"EMEA (CPMP). 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