The Effect of Metformin on Vestibular Schwannoma Growth: Systematic Review and Meta-Analysis

Objectives: Recent literature has shown variable effects of metformin use on growth of sporadic vestibular schwannomas (VS). This study was conducted to systematically review and evaluate metformin's potential impact on VS growth.

Methods: A retrospective cohort study was performed on all patients with radiographically confirmed sporadic VS who elected for initial observation and had at least two magnetic resonance imaging (MRI) studies at a minimum of three months apart. Patients were stratified by use of metformin during the observation period. The primary endpoint was VS growth, defined as at least 2-mm increase in the largest diameter, between the first and last MRI studies. Survival free of tumor growth was evaluated between the metformin and non-metformin groups and compared using Cox proportional hazards regression. A meta-analysis was then performed using a fixed-effects model with relevant literature to produce a pooled odds ratio of the effect of metformin using VS growth as a binary outcome. Study heterogeneity and Cochran's Q-statistic were calculated, and Begg's funnel plot created. Finally, a power analysis was performed to direct future studies.

Results: A total of 123 patients were included, of which 17% (n = 21) were taking metformin. The median patient age was 56.6 years (range, 25.1–84.5). Slightly more patients were female (55.3%), and the majority of patients were white (82.1%). There was no statistically significant difference between groups with regard to patient age, gender, race, length of observation, and initial and final tumor measurements. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29–1.29, p = 0.19). Furthermore, multivariable logistic regression analysis did not demonstrate a statistically significant difference between groups with regards to risk of tumor growth (odds ratio=0.46, 95% CI = 0.17–1.27, p = 0.13). Moreover, a dose-effect was not observed as there was no significant association between metformin dosage and tumor growth (p = 0.307). The systematic review identified 3 studies evaluating metformin's effect on VS growth. Two studies reported odds ratio and were included in the meta-analysis. The meta-analysis demonstrated that metformin use is associated with decreased risk of VS growth (pooled odds ratio = 0.45, 95% confidence interval = 0.29–0.71). Studies demonstrated low heterogeneity and variance (I ² = 0%). A power analysis demonstrated that a total sample size of 220 patients (110 per study group) would be required to prospectively identify a true difference with ~80% power with this odds ratio.

Conclusions: Metformin use may be associated with a reduced risk of VS growth. An appropriately powered prospective study is needed to identify a true difference between groups ([Figs. 1] [2] [3]).

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Artikel online veröffentlicht:
01. Februar 2023