The Future of Somatostatin Receptor Ligands in Acromegaly

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2021 Oct 7

PMID 34618894

Citations 28

Authors

Monica R Gadelha

Luiz Eduardo Wildemberg

Leandro Kasuki

Affiliations

Soon will be listed here.

Abstract

Currently, the first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot, and nasal octreotide, may improve patients' adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788, and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.

Citing Articles

Treatment-resistant Cushing disease and acromegaly in a young woman: A case of functional pituitary macroadenoma.

Khalil I, Hossain M Radiol Case Rep. 2025; 20(4):2013-2019.

PMID: 39926265 PMC: 11802362. DOI: 10.1016/j.radcr.2025.01.010.

Differential Impact of Medical Therapies for Acromegaly on Glucose Metabolism.

Gatto F, Arecco A, Amaru J, Arvigo M, Campana C, Milioto A Int J Mol Sci. 2025; 26(2).

PMID: 39859181 PMC: 11764544. DOI: 10.3390/ijms26020465.

Update on regulation of GHRH and its actions on GH secretion in health and disease.

Montero-Hidalgo A, Del Rio-Moreno M, Perez-Gomez J, Luque R, Kineman R Rev Endocr Metab Disord. 2025; .

PMID: 39838154 DOI: 10.1007/s11154-025-09943-y.

IGF-I levels during standard Lanreotide dose predicts biochemical outcome of high-frequency regimen in acromegaly.

Chiloiro S, Giampietro A, Giambo P, Costanza F, Mattogno P, Lauretti L Pituitary. 2024; 28(1):7.

PMID: 39724447 DOI: 10.1007/s11102-024-01479-9.

A review of precision medicine in developing pharmaceutical products: Perspectives and opportunities.

Martinez-Jimenez J, Sathisaran I, Reyes Figueroa F, Reyes S, Lopez-Nieves M, Vlaar C Int J Pharm. 2024; 670:125070.

PMID: 39689830 PMC: 11781955. DOI: 10.1016/j.ijpharm.2024.125070.

References

Colao A, Ferone D, Marzullo P, Lombardi G . Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004; 25(1):102-52. DOI: 10.1210/er.2002-0022. View

Cozzi R, Attanasio R . Octreotide for acromegaly. Expert Rev Endocrinol Metab. 2019; 2(2):129-145. DOI: 10.1586/17446651.2.2.129. View

Shimon I, Adnan Z, Gorshtein A, Baraf L, Saba Khazen N, Gershinsky M . Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018; 62(2):448-455. DOI: 10.1007/s12020-018-1690-5. View

Kasuki L, Vieira Neto L, Gadelha M . Cabergoline treatment in acromegaly: cons. Endocrine. 2014; 46(2):220-5. DOI: 10.1007/s12020-014-0183-4. View

Weeke J, Christensen S, Orskov H, Kaal A, Pedersen M, Illum P . A randomized comparison of intranasal and injectable octreotide administration in patients with acromegaly. J Clin Endocrinol Metab. 1992; 75(1):163-9. DOI: 10.1210/jcem.75.1.1619006. View

Wildemberg L, Camacho A, Lyra Miranda R, Elias P, Musolino N, Nazato D . Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands. J Clin Endocrinol Metab. 2021; 106(7):2047-2056. DOI: 10.1210/clinem/dgab125. View

Fougner S, Borota O, Berg J, Hald J, Ramm-Pettersen J, Bollerslev J . The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma. Clin Endocrinol (Oxf). 2007; 68(3):458-65. DOI: 10.1111/j.1365-2265.2007.03065.x. View

Sandret L, Maison P, Chanson P . Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011; 96(5):1327-35. DOI: 10.1210/jc.2010-2443. View

Giustina A, Karamouzis I, Patelli I, Mazziotti G . Octreotide for acromegaly treatment: a reappraisal. Expert Opin Pharmacother. 2013; 14(17):2433-47. DOI: 10.1517/14656566.2013.847090. View

10.

Jaffrain-Rea M, Rotondi S, Turchi A, Occhi G, Barlier A, Peverelli E . Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations. Endocr Relat Cancer. 2013; 20(5):753-66. DOI: 10.1530/ERC-12-0322. View

11.

Mercado M, Borges F, Bouterfa H, Chang T, Chervin A, Farrall A . A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol (Oxf). 2007; 66(6):859-68. PMC: 1974838. DOI: 10.1111/j.1365-2265.2007.02825.x. View

12.

Melmed S, Bronstein M, Chanson P, Klibanski A, Casanueva F, Wass J . A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018; 14(9):552-561. PMC: 7136157. DOI: 10.1038/s41574-018-0058-5. View

13.

Coopmans E, van der Lely A, Schneiders J, Neggers S . Potential antitumour activity of pasireotide on pituitary tumours in acromegaly. Lancet Diabetes Endocrinol. 2019; 7(6):425-426. DOI: 10.1016/S2213-8587(19)30113-5. View

14.

Katznelson L, Laws Jr E, Melmed S, Molitch M, Murad M, Utz A . Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(11):3933-51. DOI: 10.1210/jc.2014-2700. View

15.

Samson S, Nachtigall L, Fleseriu M, Gordon M, Bolanowski M, Labadzhyan A . Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide. J Clin Endocrinol Metab. 2020; 105(10). PMC: 7470473. DOI: 10.1210/clinem/dgaa526. View

16.

Swanson A, Erickson D, Donegan D, Jenkins S, Van Gompel J, Atkinson J . Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly. Pituitary. 2020; 24(2):192-206. DOI: 10.1007/s11102-020-01096-2. View

17.

Ferone D, de Herder W, Pivonello R, Kros J, Van Koetsveld P, de Jong T . Correlation of in vitro and in vivo somatotropic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy. J Clin Endocrinol Metab. 2008; 93(4):1412-7. DOI: 10.1210/jc.2007-1358. View

18.

Chahal H, Trivellin G, Leontiou C, Alband N, Fowkes R, Tahir A . Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. J Clin Endocrinol Metab. 2012; 97(8):E1411-20. DOI: 10.1210/jc.2012-1111. View

19.

Hofland L, van der Hoek J, Van Koetsveld P, de Herder W, Waaijers M, Sprij-Mooij D . The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro. J Clin Endocrinol Metab. 2004; 89(4):1577-85. DOI: 10.1210/jc.2003-031344. View

20.

Tuvia S, Atsmon J, Teichman S, Katz S, Salama P, Pelled D . Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab. 2012; 97(7):2362-9. DOI: 10.1210/jc.2012-1179. View