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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., (© 2018 European Society of Endocrinology)

Aim: To assess the efficacy and safety of pasireotide long-acting release (PAS-LAR) alone or in combination with pegvisomant by switching patients with acromegaly who were well controlled with long-acting somatostatin analogues (LA-SSAs) and pegvisomant to PAS-LAR with or without pegvisomant., Methods: Sixty-one patients with acromegaly were enrolled in a prospective open-label study. We included patients with an insulin-like growth factor I (IGF-I) ≤1.2 × upper limit of normal (ULN) during treatment with LA-SSAs and pegvisomant. At baseline, the pegvisomant dose was reduced by 50% up to 12 weeks. When IGF-I remained ≤1.2 × ULN after 12 weeks, patients were switched to PAS-LAR 60 mg monotherapy. When IGF-I was >1.2 × ULN, patients were switched to PAS-LAR 60 mg, and they continued with the 50% reduced pegvisomant dose., Results: At baseline, mean IGF-I was 0.97 × ULN, and the median pegvisomant dose was 80 mg/wk. At 12 weeks, mean IGF-I increased to 1.59 × ULN, and IGF-I levels ≤1.2 ULN were observed in 24.6% of participants. At 24 weeks, IGF-I levels were reduced into the reference range in 73.8% of patients. Between baseline and 24 weeks, the pegvisomant dose was reduced by 66.1%. PAS-LAR was well tolerated, but hyperglycemia was the most frequent adverse event. The frequency of diabetes increased from 32.8% at baseline to 68.9% at 24 weeks., Conclusions: Switching to PAS-LAR, either as monotherapy or combination with pegvisomant, can control IGF-I levels in most patients. PAS-LAR demonstrated a pegvisomant-sparing effect of 66% compared with the combination with LA-SSAs. Hyperglycemia was the most important safety issue., (Copyright © 2017 Endocrine Society)