Drug Repurposing for Reducing the Size of Benign Thyroid Nodules: A Systematic Review.

[CONTEXT] Benign thyroid nodules (BTNs) are highly prevalent, and current treatment options are primarily invasive. There is a need for effective, noninvasive alternatives.

[OBJECTIVE] To systematically evaluate the efficacy of repurposed pharmacologic agents in reducing the size of BTNs.

[DATA SOURCES] MEDLINE, EMBASE, Cochrane databases, and Scopus were searched from inception to December 18, 2024.

[STUDY SELECTION] We included preclinical and clinical studies evaluating repurposed drugs for BTNs in adults. Of 1499 records screened, 20 studies met inclusion criteria: 6 randomized controlled trials (RCTs), 6 prospective cohorts, 3 retrospective observational studies, 3 case reports, 1 cross-sectional study, and 1 preclinical study.

[DATA EXTRACTION] Data were extracted independently in duplicate using a standardized form.

[DATA SYNTHESIS] Narrative synthesis was conducted due to heterogeneity. Metformin was the most frequently evaluated agent (7 studies), with 5 studies (including 2 RCTs) reporting statistically significant reductions in dominant nodule volume. One prospective study demonstrated a reduction in the maximum nodule diameter, which was not statistically significant, and 1 RCT showed no changes in nodule size after intervention. Statins (4 studies) and somatostatin analogues (4 studies) showed mixed results. Myo-inositol with selenium, herbal formulations, and immune checkpoint inhibitors showed promise in single studies or case reports.

[CONCLUSION] Metformin shows the most consistent potential for noninvasive reduction of BTN size, particularly in patients with metabolic comorbidities. However, current evidence is limited and heterogeneous. Further large-scale studies are needed to confirm efficacy and guide clinical use.