Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2892-2902. doi: 10.1210/jc.2018-02281.

Abstract

Introduction: Pegvisomant (PEG) in monotherapy or combined with somatostatin analogs (SSAs) is used to control acromegaly, improving metabolism. However, the metabolic changes induced by PEG have not been systematically reviewed.

Objective: To address the following questions: does PEG or the combination of PEG and SSAs affect fasting plasma glucose (FPG), glycosylated Hb (HbA1c), glucose load (2-hour oral glucose tolerance test), insulin levels [fasting plasma insulin (FPI)], homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of β-cell function, lipid profile, or body mass index? Are the effects disease-related or drug-related?

Data sources: Indexed databases up to January 2019.

Study selection: Prospective interventional trials reporting glycometabolic outcomes under PEG or PEG plus SSAs for a minimum of 6 months.

Data extraction: Three reviewers screened eligible publications (7248), three others extracted the outcomes, and all assessed the risk of biases.

Data synthesis: Thirteen studies were included in the PEG and 5 in the PEG plus SSAs analysis (overall 550 subjects). PEG significantly decreased FPG [effect size (ES) -0.80 mmol/L (95% CI, -1.06 to -0.55); P = 0.000], HbA1c [ES -0.43% (95% CI, -0.56 to -0.31); P = 0.000], FPI [ES -5.31 mU/L (95% CI, -10.23 to -0.39); P = 0.034], and HOMA-I [ES -0.61 (95% CI, -1.17 to -0.04); P = 0.034]. Effects on FPG and FPI were not correlated to IGF-1 changes. The addition of PEG to SSAs mitigated the effects of SSAs on metabolism, producing an overall neutral effect.

Conclusions: Independently of disease control, PEG in monotherapy or combined with SSAs seems to improve glucose metabolism, reducing FPG, HbA1c, FPI, and HOMA-I.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy*
  • Acromegaly / metabolism
  • Blood Glucose / metabolism
  • Body Mass Index
  • Cholesterol / metabolism
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism
  • Drug Therapy, Combination
  • Glucose Tolerance Test
  • Glycated Hemoglobin / metabolism
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin Resistance
  • Octreotide / therapeutic use
  • Peptides, Cyclic / therapeutic use
  • Receptors, Somatotropin / antagonists & inhibitors
  • Somatostatin / analogs & derivatives*
  • Somatostatin / therapeutic use
  • Triglycerides / metabolism

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Peptides, Cyclic
  • Receptors, Somatotropin
  • Triglycerides
  • hemoglobin A1c protein, human
  • lanreotide
  • Human Growth Hormone
  • Somatostatin
  • Cholesterol
  • pegvisomant
  • Octreotide