Effects of short-term metformin therapy associated with levothyroxine dose decrement on TSH and thyroid hormone levels in patients with thyroid cancer.

Aim: Suppressive therapy with levothyroxine is the main step in treatment of differentiated thyroid cancer (DTC). However, subclinical hyperthyroidism is associated with deleterious effects on cardiovascular and skeletal systems. Metformin may have a suppressive effect on TSH level.

Methods: We performed a single blind randomized controlled trial on the effect of short term Metformin therapy on 50 non-diabetic patients with DTC (mean age of 39.68 ±8.7 years) under suppressive therapy with levothyroxine. Metformin (500 mg) or placebo was added to the drug regimen of the patients and levothyroxine dose decreased by 33%. TSH and thyroid hormone values were measured at the beginning of the study and 3 months after treatment.

Results: Forty-six patients had papillary and 4 had follicular carcinoma. The mean dose of levothyroxine was 2.2±0.48 µg/kg. The mean TSH level at the beginning of the study was 0.05±.04 mIU/L. The mean age, weight and baseline TSH level was not significantly different between metformin and placebo groups (P>0.2). In the metformin group, the mean (±SD) TSH level was significantly increased from 0.03±0.04 to 3.1±5.7 mIU/L after 3 months of intervention (P=0.01) and the mean thyroid hormone levels were significantly decreased (P<0.001). In the placebo group, the mean TSH level increased from 0.04±0.04 to 3.1±4.7 mIU/L after 3 months (P=0.003). Delta TSH was 3.0±5.6 mIU/L and 3.1±4.7 mIU/L in metformin and placebo groups, respectively (P=0.9).

Conclusion: Adding 500 mg of metformin to drug regimen was not useful to compensate for 33% of levothyroxine dose reduction in patients with DTC.