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.
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 acromegalypatients, 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.
Authors: Adrian F Daly; David A Cano; Eva Venegas-Moreno; Patrick Petrossians; Elena Dios; Emilie Castermans; Alvaro Flores-Martínez; Vincent Bours; Albert Beckers; Alfonso Soto-Moreno Journal: Endocr Connect Date: 2019-04 Impact factor: 3.335
Authors: Maria Fleseriu; Beverly M K Biller; Pamela U Freda; Monica R Gadelha; Andrea Giustina; Laurence Katznelson; Mark E Molitch; Susan L Samson; Christian J Strasburger; A J van der Lely; Shlomo Melmed Journal: Pituitary Date: 2020-10-20 Impact factor: 4.107
Authors: Przemysław Witek; Marek Bolanowski; Katarzyna Szamotulska; Agnieszka Wojciechowska-Luźniak; Aleksandra Jawiarczyk-Przybyłowska; Marcin Kałużny Journal: Front Endocrinol (Lausanne) Date: 2021-03-10 Impact factor: 5.555
Authors: Eva C Coopmans; Nour El-Sayed; Jan Frystyk; Nils E Magnusson; Jens O L Jørgensen; Aart-Jan van der Lely; Joop A M J L Janssen; Ammar Muhammad; Sebastian J C M M Neggers Journal: Endocrine Date: 2020-04-24 Impact factor: 3.633
Authors: Annamaria Colao; Marcello D Bronstein; Thierry Brue; Laura De Marinis; Maria Fleseriu; Mirtha Guitelman; Gerald Raverot; Ilan Shimon; Jürgen Fleck; Pritam Gupta; Alberto M Pedroncelli; Mônica R Gadelha Journal: Eur J Endocrinol Date: 2020-06 Impact factor: 6.664