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The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin\/other permitted oral antidiabetic drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Multicenter, randomized, open-label, Phase IV study comprising a core phase (\u2264\u200916-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n\u2009=\u2009190) or Cushing\u2019s disease (n\u2009=\u200959) received long-acting (starting 40\u00a0mg IM\/28 days) or subcutaneous pasireotide (starting 600\u00a0\u00b5g bid), respectively. Patients with increased fasting plasma glucose (\u2265\u2009126\u00a0mg\/dL on three consecutive days) during the 16-week pre-randomization period despite metformin\/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followed by liraglutide) or insulin for another 16\u00a0weeks. The primary objective was to evaluate the difference in mean change in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      from randomization to end of core phase between incretin-based therapy and insulin treatment arms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighty-one (32.5%) patients were randomized to incretin-based therapy (n\u2009=\u200938 received sitagliptin, n\u2009=\u200928 subsequently switched to liraglutide; n\u2009=\u200912 received insulin as rescue therapy) or insulin (n\u2009=\u200943). Adjusted mean change in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      between treatment arms was \u2013 0.28% (95% CI \u2013 0.63, 0.08) in favor of incretin-based therapy. The most common AE other than hyperglycemia was diarrhea (incretin-based therapy, 28.9%; insulin, 30.2%). Forty-six (18.5%) patients were managed on metformin (n\u2009=\u200943)\/other OAD (n\u2009=\u20093), 103 (41.4%) patients did not require any oral antidiabetic drugs and 19 patients (7.6%) were receiving insulin at baseline and were not randomized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Many patients receiving pasireotide do not develop hyperglycemia requiring oral antidiabetic drugs. Metformin is an effective initial treatment, followed by incretin-based therapy if needed.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>ClinicalTrials.gov ID<\/jats:bold>\n                      : NCT02060383.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11102-021-01161-4","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T08:02:31Z","timestamp":1626595351000},"page":"887-903","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study"],"prefix":"10.1007","volume":"24","clinical-trial-number":[{"clinical-trial-number":"nct02060383","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-7093","authenticated-orcid":false,"given":"Susan L.","family":"Samson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Witek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Kalra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto M.","family":"Pedroncelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pultar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Jabbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Bolanowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,18]]},"reference":[{"issue":"1","key":"1161_CR1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1042-3680(02)00035-9","volume":"14","author":"N Sanno","year":"2003","unstructured":"Sanno N, Teramoto A, Osamura RY, Horvath E, Kovacs K, Lloyd RV, Scheithauer BW (2003) Pathology of pituitary tumors. 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UF-R: Lecture fees from Novartis, Ipsen, Novo Nordisk, Pfizer. PW: Lecture fees from Novartis, Ipsen, Pfizer, Sanofi-Aventis, Elli-Lilly, Boehringer Ingelheim. PK: Participated in advisory board meetings of Novo Nordisk, Novartis, Eli Lilly. AMP, PP, NJ, MP: Employees of Novartis Pharmaceuticals Corporation\/Novartis Pharma AG. MB: Lecture fees from Ipsen, Pfizer, Novartis. FG, SZ, YY: Nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki, with an independent ethics committee\/institutional review board at each site approving the study protocol.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients provided written informed consent before participation.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}