Effects of Metformin on Thyroid Function in Patients with Type 2 Diabetes, Subclinical Hypothyroidism, and Insulin Resistance: A Systematic Review and Meta-Analysis
Hossein Nezami, Alireza Amirabadizadeh, Mahdi Abdesheikhi, Ahmadreza Baghestani, Habibollah EsmailyIntroduction/Objective:
Metformin, the first-line therapy for type 2 diabetes and insulin resistance, has been reported to affect thyroid function, particularly Thyrotropin (TSH), although results for other thyroid hormones are inconsistent. We therefore performed a systematic review and meta-analysis to evaluate the effects of metformin on serum TSH, FT4, FT3, total T4, and total T3 levels compared with placebo in patients with type 2 diabetes, insulin resistance, and subclinical hypothyroidism.
Methods:
A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted from inception to November 2025 to identify randomized controlled trials and observational studies evaluating the effects of metformin on thyroid hormone parameters compared with placebo. Pooled mean differences with 95% confidence intervals were calculated using random-effects models. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using Begg’s test. Sensitivity analyses were performed to assess the robustness of the pooled estimates.
Results:
A total of 13 studies including 1,178 participants were included in the meta-analysis. In patients with type 2 diabetes, metformin therapy was associated with a statistically significant reduction in serum FT3 concentrations compared with placebo (MD= −0.44; 95% CI: −0.79 to −0.10; p = 0.01), whereas no significant change in serum TSH levels was observed (MD = −0.38; 95% CI: −1.05 to 0.41; p = 0.39); FT4 and total T4 levels also remained unchanged. Among patients with subclinical hypothyroidism, metformin treatment was not associated with significant changes in TSH or FT4 concentrations.
Discussion:
Metformin appears to have limited effects on thyroid-related parameters in patients with type 2 diabetes and subclinical hypothyroidism. The observed reduction in FT3 levels, in the absence of consistent changes in TSH or FT4, may indicate that the changes observed in thyroid hormone profiles are limited and should be interpreted considering the clinical context and variability among included studies.
Conclusion:
Current evidence suggests that metformin does not significantly modify overall thyroid function in patients with type 2 diabetes, subclinical hypothyroidism, or insulin resistance. Further studies are needed to clarify its potential effects in specific patient populations.