Influence of Metformin on Thyroid Architecture and Hormonal Homeostasis in Experimental Rats

Author(s): Rusul Ali Kadhim
Date: 09/10/2026
doi: https://doi.org/10.5281/zenodo.8425890

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Abstract

Background: Metformin is widely known as a drug for controlling type 2 diabetes; however, 
the impact of metformin on thyroid function has not been sufficiently studied. The objective of 
this study was to investigate the role of metformin on thyroid glands and hormonal levels in 
rats.  
Methods: Forty-eight Wistar rats were placed in control groups (n=12), groups treated with 
metformin in small doses (n=12), groups treated with metformin in medium doses (n=12) and 
groups treated with metformin in high doses (n=12) for 12 weeks. TSH, FT4, and FT3 were 
assessed in sera by radioimmunoassay. The architecture of thyroid glands was studied using 
histopathological and morphometric methods.  
Results: The rats treated with metformin had improved thyroid architecture in a dose-related 
manner and better preservation of colloids in their thyroids. The level of TSH in the sera 
decreased significantly in the groups treated with metformin in a high dose (0.52±0.12 mIU/L 
as compared to 1.24±0.18 mIU/L, p<0.05), while the levels of FT4 and FT3 increased 
moderately. The follicle diameter and epithelial cell height increased in a dose-dependent 
manner (18-22% and 51% respectively), predominantly due to enhanced colloid accumulation 
(58.4% to 78.6%) rather than cellular proliferation, consistent with metformin's antiproliferative 
effects. 
Conclusion: Metformin protects thyroid architecture and maintains hormonal levels in rats; it 
may have some additional beneficial effects apart from controlling blood glucose level. 

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