{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:35:05Z","timestamp":1792643705955,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the efficacy and safety after 48 weeks of treatment with pasireotide long-acting-release (PAS-LAR) alone or in combination with pegvisomant in patients with acromegaly. In addition, we assessed the relation between insulin secretion and pasireotide-induced hyperglycemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>The PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty-nine out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (\u22641.2\u00d7 the upper limit of normal (ULN)) at 48 weeks through protocol-based adjustment of pegvisomant and PAS-LAR doses. At baseline, insulin secretion was assessed by an oral glucose tolerance test (OGTT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the end of the study, median IGF-I was 0.98\u00d7 ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64\u2009mg\/week, and an overall cumulative pegvisomant dose reduction of 52%. Frequency of diabetes mellitus increased from 68% at 24 weeks to 77% at 48 weeks, and nine patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.37,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PAS-LAR normalizes IGF-I levels in most acromegaly patients, with a 50% pegvisomant-sparing effect. However, PAS-LAR treatment coincided with a high incidence of diabetes mellitus. The risk for developing diabetes during PAS-LAR treatment seems inversely related to insulin secretion at baseline.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-18-0353","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T12:45:18Z","timestamp":1533300318000},"page":"269-277","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":49,"title":["Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somatostatin analogues: PAPE extension study"],"prefix":"10.1093","volume":"179","author":[{"given":"Ammar","family":"Muhammad","sequence":"first","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva C","family":"Coopmans","sequence":"additional","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patric J D","family":"Delhanty","sequence":"additional","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alof H G","family":"Dallenga","sequence":"additional","affiliation":[{"name":"2Department of Neurosurgery, Pituitary Center Rotterdam, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain K","family":"Haitsma","sequence":"additional","affiliation":[{"name":"2Department of Neurosurgery, Pituitary Center Rotterdam, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A M J L","family":"Janssen","sequence":"additional","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aart J","family":"van der Lely","sequence":"additional","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian J C M M","family":"Neggers","sequence":"additional","affiliation":[{"name":"1Endocrinology Section, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref51","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1210\/jc.2012-3072","article-title":"A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy","volume":"98","year":"2013","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref71","first-page":"1282","article-title":"Tumor shrinkage with lanreotide autogel 120\u2009mg as primary therapy in acromegaly: results of a prospective multicenter 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