title: Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly.
abstract: The purpose of this study was to gain more insight into the mechanism of action of pasireotide in patients who completed the PAOLA study. PAOLA was a 24-week, Phase III, randomized, three-arm study of pasireotide LAR 40 and 60 mg versus octreotide LAR 30 mg or lanreotide Autogel 120 mg in patients with inadequately controlled acromegaly. The current work was a planned exploratory objective of the PAOLA study that evaluated changes in levels of growth hormone (GH), insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBP-2, IGFBP-3), glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in each treatment arm. Responders to pasireotide LAR (mean GH levels <2.5 μg/L and normal IGF-1 levels at 24 weeks) had lower GH and IGF-1 levels at baseline (GH 5.1 ng/mL, IGF-1 519 ng/mL) than non-responders (GH 7.9 ng/mL, IGF-1 672 ng/mL). Frequency of hyperglycaemia after pasireotide treatment was similar in responders and non-responders and depended more on the baseline FPG level. 47 % of all patients treated with pasireotide LAR (40 or 60 mg) did not receive antidiabetic medication at any time during this study. This is the first study to evaluate the treatment effect of pasireotide on key hormonal and glycaemic biomarkers and to identify potential predictors of pasireotide-associated hyperglycaemia. Pre-treatment glucose status may be predictive of the development of pasireotide-associated hyperglycaemia. A large subset of patients with acromegaly does not experience major disturbances in glucose homeostasis while receiving pasireotide LAR.
authors.affiliation: Novartis Pharma AG, Postfach, Basel, Switzerland. herbert.schmid@novartis.com.
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Schmid
authors.affiliation: Centre National de la Recherche Scientifique, and Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, Aix-Marseille University, Marseille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
authors.affiliation: Università Federico II di Napoli, Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.affiliation: Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
authors.affiliation: Institute of Endocrinology and Metabolism, Rabin Medical Center, and Sackler School of Medicine, Tel-Aviv University, Petah Tikva, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Shimon
authors.affiliation: Novartis Pharma AG, Postfach, Basel, Switzerland.
authors.forename: Karen
authors.initials: K
authors.lastname: Kapur
authors.affiliation: Novartis Pharma AG, Postfach, Basel, Switzerland.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pedroncelli
authors.affiliation: Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Fleseriu
mesh_terms: D000172:Acromegaly / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D019233:Retreatment; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D015282:Octreotide; D010456:Peptides, Cyclic; D013004:Somatostatin; C515497:IGFBP3 protein, human; C060347:lanreotide; C517782:pasireotide
keywords: Acromegaly; Glucose; HbA1c; Hyperglycaemia; PAOLA; Pasireotide