Hyperglycemia induced by pasireotide in patients with Cushing's disease or acromegaly

Julie M Silverstein, Julie M Silverstein

Abstract

Purpose: Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia.

Methods: Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed.

Results: The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues.

Conclusions: Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation.

Keywords: Acromegaly; Cushing’s disease; Hyperglycemia; Pasireotide.

Conflict of interest statement

JMS has received research support from Ipsen Biopharmaceuticals, Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk, and Pfizer. She is on the speaker’s bureau for Pfizer and Chiasma and has been on an advisory board for Chiasma, Ipsen Biopharmaceuticals, and Corcept. Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Factors potentially affecting reported differences in a the frequency of pasireotide-induced hyperglycemia and b the frequency of discontinuations associated with hyperglycemia among patients with CD or acromegaly. AE adverse event, CD Cushing’s disease, LAR long-acting release, SC subcutaneous. Figure was created with Adobe Illustrator CC 2015

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