Long-term safety and efficacy of long-acting pasireotide in acromegaly

Akirov, Amit; Gorshtein, Alexander; Dotan, Idit; Khazen, Nariman Saba; Pauker, Yulia; Gershinsky, Michal; Shimon, Ilan

doi:10.1007/s12020-021-02782-2

Cited by 14 publications

(2 citation statements)

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“…Half of them required an antidiabetic treatment, whereas the other half was on dietary regimen only. These findings extend recently published observations from real-life clinical settings in short- ( 35 ) and long-term follow-up ( 36 ). In approximately one-quarter of our patients, treatment with pasireotide was stopped due to worsening of glycemic control, which is markedly higher than the dropout rates in prospective clinical trials ( 12 , 14 , 37 ).…”

Section: Discussionsupporting

confidence: 90%

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR

Wolf

Dormoy

Maione

et al. 2022

Endocrine Connections

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Objective: Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effects on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. Design: We performed a retrospective study. Methods: Efficacy (GH/IGF-I concentrations; tumor size) and effects on glucose homeostasis were analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean±SD, 6.1±3.8 months) and on long term (24.4±11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (Insulinogenic index; Disposition index) and insulin sensitivity were calculated by validated indices. Results: Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term [Insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; p=0.028; Disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; p=0.024]. No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-I concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Conclusion: Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of anti-diabetic treatment for pasireotide induced hyperglycemia.

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Section: Discussionsupporting

confidence: 90%

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR

Wolf

Dormoy

Maione

et al. 2022

Endocrine Connections

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“…Despite our study was not being designed to provide data of efficacy of second line therapies, we found that at the follow-up last visit, the control of acromegaly was reached in 22 patients treated with m-Peg-V (66.7%), in 22 patients treated with c-Peg-V (63.9%) and in 25 patients treated with Pasireotide Lar (74.2%). These data are superimposable to those observed in previous series, as the reaching of acromegaly control is reported from 64% to 97% of patients treated with Peg-V in long term follow-up [24][25][26][27][28][29][30][31][32][33][34][35]. This magnitude in the percentage of patients who reached the control of acromegaly by second line therapies may be justified by the different study design (such as clinical trials, randomized or real life studies) and from the dosage of therapies.…”

Section: Discussionsupporting

confidence: 63%

Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly

et al. 2022

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Introduction Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. Patients and methods A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). Results Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). Conclusion Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.

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