Journal of Endocrinological Investigation

, Volume 42, Issue 12, pp 1451–1458 | Cite as

Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial

  • R. Palui
  • J. Sahoo
  • S. KamalanathanEmail author
  • S. S. Kar
  • K. Sridharan
  • H. Durgia
  • H. Raj
  • M. Patil
Original Article



Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH).


In this open label, parallel arm, randomised controlled trial, 60 patients of SCH (TSH 5.5–10 mIU/L) were randomised to either metformin group (1500 mg/day) or control group.


A total of 46 patients (23 in each group) completed the study and no significant difference in serum TSH, free T4 or free T3 was found in between the 2 groups. Neither there was any significant change in serum TSH, free T4 or free T3 (pre and post 6 months) within the individual groups. However, the rate of normalisation of serum TSH in patients with negative thyroid antibody was significantly higher than patients with positive thyroid antibody (71.4% vs. 18.8%; P = 0.026) in metformin group in post hoc analysis. Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group. Four patients (17%) had mild gastrointestinal adverse effects in the metformin group.


We did not find any significant change in thyroid function test in patients with SCH with metformin therapy.


Adipokines Insulin resistance Metformin Subclinical hypothyroidism 


Anti-Tg Ab

Anti-thyroglobulin antibody

Anti-TPO Ab

Anti-thyroid peroxidase antibody


Body mass index


Confidence interval


Diastolic blood pressure


Diabetes mellitus


Free T3


Free T4


High-density lipoprotein


Homeostasis Model Assessment for 2 Insulin Resistance


Inter-quartile range


Insulin resistance


Low-density lipoprotein


Polycystic ovarian disease


Quantitative Insulin Sensitivity Check Index


Randomised controlled trial


Systolic blood pressure


Subclinical hypothyroidism


Standard deviation


Thyroid function test


Thyroid stimulating hormone


Very-low-density lipoprotein


Waist circumference



This study was done from intramural research fund (Grant number: JIP/Res/Intra-DM-MCH/phs1/01/2016-17 Project number 37) of Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interests.

Ethical approval

This study was done with approval of Institute ethical committee.

Informed consent

Informed consent was obtained from all individual human participants included in the study.

Supplementary material

40618_2019_1059_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)


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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Department of EndocrinologyJIPMERPuducherryIndia
  2. 2.Department of Preventive and Social MedicineJIPMERPuducherryIndia
  3. 3.Inlaks Budhrani HospitalPuneIndia

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