Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies.
Level 1 - systematic review of randomized trials
Meta-analysis of prospective interventional studies
PubMed 30869797 · doi:10.1210/jc.2018-02281
What was done
A systematic review and meta-analysis of indexed databases through January 2019 evaluated prospective interventional trials lasting at least 6 months that reported glycometabolic outcomes with pegvisomant (PEG) monotherapy or PEG combined with somatostatin analogs (SSAs) in patients with acromegaly. Reviewers assessed fasting plasma glucose (FPG), HbA1c, 2-hour oral glucose tolerance test, fasting plasma insulin (FPI), HOMA-IR (HOMA-I), HOMA-beta, lipid profiles, and body mass index across 13 PEG studies and 5 PEG plus SSA studies covering 550 patients.
What was found
PEG monotherapy significantly improved several glycemic markers: - FPG decreased: effect size (ES) -0.80 mmol/L (95% CI, -1.06 to -0.55; P = 0.000). - HbA1c decreased: ES -0.43% (95% CI, -0.56 to -0.31; P = 0.000). - FPI decreased: ES -5.31 mU/L (95% CI, -10.23 to -0.39; P = 0.034). - HOMA-I decreased: ES -0.61 (95% CI, -1.17 to -0.04; P = 0.034). Reductions in FPG and FPI were not correlated with changes in IGF-1. Combining PEG with SSAs mitigated SSA-induced metabolic disruptions, resulting in an overall neutral effect on glucose metabolism. Numerical results for 2-hour OGTT, HOMA-beta, lipids, and BMI were not reported in the abstract.
Why it matters
This indicates that pegvisomant directly improves glucose metabolism and insulin sensitivity in acromegaly rather than simply acting through systemic IGF-1 reduction. It also demonstrates that adding pegvisomant can counterbalance the glycemic worsening frequently seen with somatostatin analog therapy.
Limits
The total sample size was modest (550 subjects across 18 studies). The abstract does not distinguish between randomized controlled trials and non-randomized single-arm interventional cohorts, nor does it provide numerical data for lipid changes, body mass index, or oral glucose tolerance test outcomes.