OBJECTIVE: 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.DESIGN: The PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks.METHODS: 59 out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (≤ 1.2 x 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).RESULTS: At the end of the study median IGF-I was 0.98 x ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64 mg/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 9 patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (r = -0.37, P < 0.005).CONCLUSIONS: PAS-LAR normalizes IGF-I levels in most acromegaly patients, with a fifty percent 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.

doi.org/10.1530/EJE-18-0353, hdl.handle.net/1765/111169
European Journal of Endocrinology
Department of Internal Medicine

Muhammad, A., Coopmans, E.C. (Eva C.), Delhanty, P., Dallenga, A. H. G., Haitsma, I., Janssen, J.A.M.J.L. (Joseph A M J L), … Neggers, B. (2018). Efficacy and Safety of switching to Pasireotide in Acromegaly Patients controlled with Pegvisomant and Somatostatin Analogues: PAPE extension study. European Journal of Endocrinology, 179(5), 269–277. doi:10.1530/EJE-18-0353