Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin Resistance: A Systematic Review and Meta-Analysis

Abstract

Background: To evaluate the effect of metformin therapy on decreasing benign thyroid nodule volume in subjects with insulin resistance (IR).Method: Randomized controlled trials (RCTs) and self-controlled trials for the meta-analysis published, before January 31, 2018 were selected from the PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, National Knowledge Infrastructure, WANFANG and VIP Database. Pooled standard mean difference with 95% confidence interval was estimated by fixed- or random-effects model depending on heterogeneity. The risk of bias using the Cochrane Collaboration's tool was used to assess the quality of the RCTs contained. The quality of self-controlled studies was evaluated using the Methodological index for non-randomized studies (MINORS) method.Results: 7 studies (3 RCTs and 4 prospective self-controlled studies) with 240 patients were considered to be appropriate for the meta-analysis. The results of the meta-analysis indicated that the volume of thyroid nodule decreased significantly after metformin therapy (SMD −0.62, 95% CI −0.98 ~ −0.27). 6 studies reported the changes of the level of TSH. TSH levels decreased significantly after metformin therapy (SMD −0.27, 95% CI −0.47 ~ −0.07). The pooled data indicated an increase in FT3 level, and an unchanged FT4 level after metformin therapy (FT3, SMD 0.25, 95% CI 0.05 ~ 0.45; FT4, SMD −0.07, 95% CI −0.27 ~ 0.13). HOMA-IR levels decreased significantly after metformin therapy based on the pooled results of 3 RCTs and 3 prospective self-controlled studies (SMD −1.08, 95% CI −1.69 ~ −0.47).Conclusion: The meta-analysis demonstrated that metformin was safe and useful in shrinking benign thyroid nodules volume, improving thyroid function and IR. A large number of high-quality prospective studies still need to be carried out.

The role of an anti-diabetic drug metformin in the treatment of endocrine tumors

“…In a recently published meta-analysis study that included 240 patients from three randomized control trials and four prospective studies, metformin treatment caused a decrease in nodular volume, TSH level and improvement in the insulin resistance in these patients (Sui et al 2018). Another very recent meta-analysis, including 189 patients fulfilling the analysis criteria, provided similar conclusions (He et al 2019).…”

Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency

“…Rezzónico et al (6) reported the effect of MTF on reduction in nodular size in patients with small benign TN and IR after 6 months of follow-up. Recently, two meta-analysis demonstrated a significant decrease in TN volume after MTF therapy by pooling the results of smaller studies (9, 10). Miao et al (9) included seven studies with a total of 240 subjects and He et al (10) included five studies with a total of 189 subjects.…”

“…Recently, two meta-analysis demonstrated a significant decrease in TN volume after MTF therapy by pooling the results of smaller studies (9, 10). Miao et al (9) included seven studies with a total of 240 subjects and He et al (10) included five studies with a total of 189 subjects. The time of follow-up in these studies ranged from 3 to 12 months.…”

“…The present study has certain limitations. Our sample was small, which might have limited the statistical power of the analysis; however, this was also a limitation for other randomized controlled trials included in the meta-analysis (9, 10). Rezzónico et al (6) evaluated 14 patients in MTF group (19 TNs), and Karimifar et al (8) included 43 subjects in the MTF group (35 TNs).…”

“…The follow-up time (6 months) might have been insufficient to observe a reduction in nodular goiter size; however, the follow-up period in the majority of studies included in the meta-analysis was 6 months. Only one study had a 1 year follow-up time (9, 10).…”