{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:18:49Z","timestamp":1792930729253,"version":"4.5.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type 2 diabetes, have caused hyperplasia\/neoplasia of thyroid C cells in rodent carcinogenicity studies. Studies in monkeys have not identified an effect of GLP-1 receptor agonists on thyroid C cells; however, group sizes were small. Dulaglutide is a once-weekly, long-acting human GLP-1 receptor agonist recently approved in the United States and the European Union. The objective of this study was to determine whether dulaglutide altered C-cell mass in monkeys. Male cynomolgus monkeys (20 per group) were sc injected with dulaglutide 8.15 mg\/kg (\u223c500-fold maximum human plasma exposure) or a vehicle control twice weekly for 52 weeks. Basal and calcium gluconate-stimulated serum calcitonin concentrations were obtained at 3, 6, 9, and 12 months. Thyroid glands were weighed, fixed, and sectioned at 500-\u03bcm intervals. C-cell volumes were measured using an automated image analysis. C-cell proliferation was estimated using Ki67\/calcitonin colabeling and cell counting. Administration of dulaglutide 8.15 mg\/kg twice weekly for 52 weeks did not increase serum calcitonin in monkeys or affect thyroid weight, histology, C-cell proliferation, or absolute\/relative C-cell volume. This study represents a comprehensive evaluation of the monkey thyroid C cells after dosing with a GLP-1 receptor agonist, with a large group size, and measurement of multiple relevant parameters. The lack of effect of dulaglutide on C cells is consistent with other studies in monkeys using GLP-1 receptor agonists and suggests that nonhuman primates are less sensitive than rodents to the induction of proliferative changes in thyroid C cells by GLP-1 receptor agonists.<\/jats:p>","DOI":"10.1210\/en.2014-1717","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T01:03:44Z","timestamp":1428714224000},"page":"2409-2416","source":"Crossref","is-referenced-by-count":15,"title":["Effects of Dulaglutide on Thyroid C Cells and Serum Calcitonin in Male Monkeys"],"prefix":"10.1210","volume":"156","author":[{"given":"John L.","family":"Vahle","sequence":"first","affiliation":[{"name":"Department of Toxicology, Pathology, and Drug Disposition (J.L.V., R.A.B., J.L.B., J.A.M., J.A.W., H.W.S.), Indianapolis, Indiana 46285"},{"name":"Eli Lilly and Company (J.L.V., R.A.B., J.L.B., J.A.M., J.A.W., H.W.S.), Indianapolis, Indiana 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