Skip to main content
SpringerLink
Log in

Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Several recent studies have reported beneficial effects of pegvisomant monotherapy on glucose homeostasis for acromegalic patients resistant to somatostatin analogs (SSA). The aim of our longitudinal study was to test whether these beneficial effects on glucose homeostasis would also occur during combined pegvisomant + SSA treatment amongst partially SSA-resistant acromegalic patients. Ten non-diabetic, partially SSA-resistant acromegalic patients underwent a 12-month SSA+pegvisomant treatment after SSA-only therapy. Glucose homeostasis was evaluated at disease diagnosis, at the end of the SSA treatment and after 6 and 12 months of combined SSA+pegvisomant treatment. The addition of pegvisomant treatment was accompanied by a significant improvement in insulin and glycemic responses to the oral glucose tolerance test, without any significant changes in fasting plasma glucose, glycosylated haemoglobin, homeostatic model assessment-derived insulin resistance index and homeostatic model assessment-derived β-cell function. Moreover, the number of patients with glucose intolerance did not significantly change during the 12-month combined treatment, notwithstanding the significant decrease in serum IGF-1 values. Therefore, our findings suggest that the combined pegvisomant and SSA treatment may not be able to restore normal clinical and biochemical glycometabolic features occurring in acromegalic patients resistant to SSA, while a slight but significant improvement in some biochemical features may be expected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metabol 89:667–674

    Article  CAS  Google Scholar 

  2. Kauppinen-Makelin R, Sane T, Reunanen A, Valimaki MJ, Niskanen L, Markkanen H, Loyttyniemi E, Ebeling T, Jaatinen P, Laine H, Nuutila P, Salamela P, Salmi J, Stenman UH, Viikari J, Voutilainen E (2005) A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metabol 90:4081–4086

    Article  CAS  Google Scholar 

  3. Clayton RN (2003) Cardiovascular function in acromegaly. Endocrine Review 24:272–277

    Article  CAS  Google Scholar 

  4. Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocrine Rev 25:102–152

    Article  CAS  Google Scholar 

  5. Kuller LH, Velentgas P, Barzilay J, Beauchamp NJ, O’Leary DH, Savane PJ (2000) Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality. Arter Thromb Vasc Biol 20:823–829

    CAS  Google Scholar 

  6. Clemmons DR (2004) The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest 113:25–27

    Article  PubMed  CAS  Google Scholar 

  7. Giustina A, Casanueva FF, Cavagnini F, Chanson P, Clemmons D, Frohman LA, Gaillard R, Ho K, Jaquet P, Kleinberg DL, Lamberts SW, Lombardi G, Sheppard M, Strasburger CJ, Vance ML, Wass JA, Melmed S (2003) The pituitary society, the european neuroendocrine association: diagnosis and treatment of acromegaly complications J Endocrin Invest 26:1242–1247

    CAS  Google Scholar 

  8. Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A (2005) Consensus statement: medical management of acromegaly. Eur J Endocrinol 153:737–740

    Article  PubMed  CAS  Google Scholar 

  9. Freda PU, Katznelson L, van der Lely AJ, Reyes CM, Zhao S, Rabinowitz D (2005) Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metabol 90:4465–4473

    Article  CAS  Google Scholar 

  10. Baldelli R, Battista C, Legnetti F, Ghigni MR, Ribaldo MC, Paoloni A, D’Amico E, Ferretti E, Baratta R, Liuzzi A, Trischitta V, Tamburano G (2003) Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment. Clin Endocrinol 59:492–499

    Article  CAS  Google Scholar 

  11. Pereira AM, Biermasz NR, Roelfsema F, Romijn JA (2005) Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance. Treat Endocrinol 4:43–53

    Article  PubMed  CAS  Google Scholar 

  12. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barman AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N E J Med 342:1171–1177

    Article  CAS  Google Scholar 

  13. Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ (2000) Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocrine Rev 23:623–646

    Article  CAS  Google Scholar 

  14. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 24:1754–1759

    Article  Google Scholar 

  15. Stewart PM (2003) Pegvisomant: an advance in clinical efficacy in acromegaly. Eur J Endocrinol 148:S27–S32

    Article  PubMed  CAS  Google Scholar 

  16. Sesmilo G, Fairfield WP, Katznelson L, Pulaski K, Freda PU, Bonert V, Dimaraki E, Stavrou S, Vance ML, Hayden D, Klibanski A (2002) Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocrinol Metabol 87:1692–1699

    Article  CAS  Google Scholar 

  17. Drake WM, Rowles SV, Roberts ME, Fode FK, Besser GM, Monson JP, Trainer PJ (2003) Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol 149:521–527

    Article  PubMed  CAS  Google Scholar 

  18. Barkan AL, Barman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML (2005) Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metabol 90:5684–5691

    Article  CAS  Google Scholar 

  19. Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Barman P, Kourides IA, Strasburger CJ, Lombardi G (2006) Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol 154:467–477

    Article  PubMed  CAS  Google Scholar 

  20. Jorgensen JO, Feldt-Rasmussen U, Frystyk J, Chen JW, Kristensen LO, Hagen C, Orskov H (2005) Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist. J Clin Endocrino Metabol 90:5627–5631

    Article  CAS  Google Scholar 

  21. Gola M, Bonadonna S, Mazziotti G, Amato G, Giustina A (2006) Resistance to somatostatin analogs in acromegaly: an evolving concept? J Endocrinol Invest 29:86–93

    PubMed  CAS  Google Scholar 

  22. Feenstra J, de Herder WW, ten Have SM, van den Beld AW, Feelders RA, Janssen JA, van der Lely AJ (2005) Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 365:1644–1646

    Article  PubMed  CAS  Google Scholar 

  23. Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Werder KV, Wass J, Giustina A (2002) Guidelines for acromegaly management. J Clin Endocrinol Metabol 87:4054–4058

    Article  CAS  Google Scholar 

  24. Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metabol 85:526–529

    Article  CAS  Google Scholar 

  25. American Diabetes Association (2006) Standards of Medical Care in Diabetes Diabetes Care 29:S4–S42

    Google Scholar 

  26. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  27. Bertoli A, Magnaterra R, Borboni P, Marini MA, Barini A, Fusco A, Bollea MR (1998) Dose-dependent effect of octreotide on insulin secretion after OGTT in obesity. Hormone Res 49:17–21

    Article  PubMed  CAS  Google Scholar 

  28. Ronchi CL, Orsi E, Giavoli C, Cappiello V, Epaminonda P, Beck-Peccoz P, Arosio M (2003) Evaluation of insulin resistance in acromegalic patients before and after treatment with somatostatin analogues. J Endocrinol Invest 26:533–538

    PubMed  CAS  Google Scholar 

  29. Parkinson C, Drake WM, Roberts ME, Meeran K, Besser GM, Trainer PJ (2002) A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. J Clin Endocrinol Metabol 87:1797–1804

    Article  CAS  Google Scholar 

  30. Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N (2000) Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrino 52:549–555

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrinology, Catholic University of Sacred Heart, Rome, Italy

    Laura De Marinis, Antonio Bianchi, Alessandra Fusco, Vincenzo Cimino, Marilda Mormando, Laura Tilaro & Alfredo Pontecorvi

  2. Endocrine Section, Department of Internal Medicine, University of Brescia, Brescia, Italy

    Gherardo Mazziotti & Andrea Giustina

Authors
  1. Laura De Marinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincenzo Cimino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marilda Mormando
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura Tilaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gherardo Mazziotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alfredo Pontecorvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea Giustina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura De Marinis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Marinis, L., Bianchi, A., Fusco, A. et al. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA. Pituitary 10, 227–232 (2007). https://doi.org/10.1007/s11102-007-0037-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-007-0037-7

Keywords

Search

Navigation