Role of Metformin in the Treatment of Patients with Thyroid Nodules and Insulin Resistance: A Systematic Review and Meta-Analysis

Background: Metformin is the most-prescribed oral medication to lower blood glucose worldwide. Some data suggest that metformin may have a role in the treatment of patients with thyroid nodules, but contrasting results are reported in different settings. This study explores and critically reevaluates the knowledge on this topic.

Methods: A literature search identified 250 records. Studies evaluating the size of thyroid nodules before and after metformin treatment were included. Assessed outcomes were the size of thyroid nodules, thyrotropin (TSH) level, thyroid gland volume, and insulin resistance index (HOMA-IR). After screening and full-text assessment, five studies were included in the systematic review. Random-effects meta-analyses of the standardized mean difference (SMD) were performed for the four outcomes of interest. Heterogeneity was estimated using I², and the quality of evidence was assessed for each outcome using the Grading of Recommendations Assessment, Development, and Evaluation guidelines.

Results: A total of 189 patients were included in the final analysis. After metformin treatment, a slight but significant reduction in thyroid nodule size was found in four studies, which included a total of 167 patients (SMD 0.46 [confidence interval (CI) 0.00-0.93]; p = 0.05). Similarly, in four studies reporting on a total of 146 patients, significant reductions in TSH level (SMD 0.30 [CI 0.07-0.53]; p = 0.01) and HOMA-IR level (SMD 0.90 [CI 0.12-1.67]; p = 0.02) were reported after treatment with metformin. In two studies, which included 114 patients, no change in thyroid gland volume was discovered after treatment with metformin (SMD 0.21 [CI -0.05 to 0.47]; p = 0.11). Quality of evidence was generally assessed as low or very low.

Conclusions: Metformin induces reductions in thyroid nodule size and TSH and HOMA-IR levels in patients with thyroid nodules and insulin resistance. In contrast, no change in thyroid gland volumes was found. Whether metformin treatment for thyroid nodules has clinical significance remains to be demonstrated.