Metformin treatment for small benign thyroid nodules in patients with insulin resistance

Metab Syndr Relat Disord. 2011 Feb;9(1):69-75. doi: 10.1089/met.2010.0026. Epub 2010 Dec 3.


Objective: It has been shown that patients with insulin resistance (IR) have a higher prevalence of thyroid nodules and bigger thyroid glands. We evaluated the ability of metformin (M) alone or combined with levothyroxine (L-T₄) to reduce the nodular size in benign thyroid hyperplastic nodules (<2 cm in diameter).

Methods: A total of 66 women with IR and nodular hyperplasia, diagnosed by fine needle aspiration biopsy (FNAB), who completed this prospective 6-month duration protocol, were assigned to one of four groups: Group I (GI) (n = 14), patients treated with M; GII (n = 18), patients treated with M plus L-T₄; GIII (n = 19), patients treated with L-T₄; and GIV (n = 15), patients without any treatment.

Results: All groups of included patients had no statistically significant different mean baseline characteristics. Patients from GII and GIII showed drops in thyroid-stimulating hormone (TSH) levels and GI and GII normalized the homeostasis model assessment (HOMA) index after treatment, as expected. The median baseline size of all included nodules was 298 mm³ ≈0.84 cm in diameter (range, 32-3,616 mm³). After treatment, patients of Group I and II showed significant reductions in their nodule size [median reduction, 108.50 mm³ (30%) and 184.5 mm³ (55%), P < 0.008 and P < 0.0001, respectively]. Patients in GIII and GIV did not have a significant reduction of their nodules [P = not significant (N.S.)].

Conclusions: We conclude that M produced a significant decrease in the nodular size in patients with IR and small thyroid nodules, whereas the combination of M with L-T₄ was the best treatment in these women.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance* / physiology
  • Metformin / administration & dosage
  • Metformin / therapeutic use*
  • Middle Aged
  • Thyroid Nodule / complications
  • Thyroid Nodule / drug therapy*
  • Thyroid Nodule / pathology
  • Thyroxine / administration & dosage
  • Tumor Burden / drug effects
  • Young Adult


  • Hypoglycemic Agents
  • Metformin
  • Thyroxine