Clinical retrospective analysis of metformin on TSH levels and nodule volume in patients with type 2 diabetes mellitus combined with thyroid nodules

Thyroid nodule (TN) prevalence is rising globally, with particularly high rates among patients with type 2 diabetes mellitus, where insulin resistance and hyperinsulinemia may promote nodule formation via the thyroid-stimulating hormone (TSH)/insulin-like growth factor-1 axis. Metformin, the standard first-line therapy for T2DM, may exert additional effects on thyroid structure beyond glycemic control. This single-center retrospective cohort study enrolled 80 patients with T2DM and benign TNs, assigned to a metformin group (n = 40) or control group (n = 40), and followed for 12 months. Changes in TSH and nodule volume were assessed using multivariable regression, propensity score matching, and sensitivity and subgroup analyses to address confounding. After 12 months, metformin treatment was associated with a significant reduction in TSH (adjusted β = -0.32, 95% confidence interval: -0.57 to -0.06, P = .017) and nodule volume (adjusted β = -8.5, 95% confidence interval: -15.9 to -1.1, P = .024). These effects were consistent in sensitivity analyses, with stronger associations observed in men, patients with body mass index < 28 kg/m², and those with glycated hemoglobin < 8%. In conclusion, metformin significantly lowers TSH levels and reduces nodule size in T2DM patients with benign TNs, supporting its potential clinical utility. Confirmation through large, multicenter, long-term prospective trials is warranted.