Long Term Effects of Metformin in a Non-Diabetic Population with Differentiated Thyroid Carcinoma

Introduction: Differentiated thyroid carcinoma (DTC) is the most frequent endocrine neoplasm. Type 2 diabetes mellitus (DMT2) and cancer share several risk factors. Metformin is used as an anti-hyperglycemic agent to reduce insulin resistance. Its anti-proliferative role is widely discussed in the literature. Materials and Methods: 95 DTC patients without a diagnosis of DMT2 (group 1), in whom metformin was started, 79 non-diabetics DTC patients who did not start metformin (group 2) served as a control group. All subjects were evaluated at the baseline and after 12 and 24 months. Group 1 was also evaluated at 3 months and 36 month to assess the tolerability of metformin and then the therapy compliance. Results: Prospective evaluation of group 1 versus group 2: no differences in the values of TSH at 24 months (P = 0.23); no differences in L-T4 dosages. No significant difference in Tg values emerged between group 1 and group 2 (P = 0.06), nor between baseline Tg and the values at 3 (P = 0.06), 12 (P = 0.1), 24 months (P = 0.25) after the start of metformin. No differences in group 1 in the values of Tg (P = 0,79) or TSH (P=0.26) between baseline and 36 months. In group 1, a significant difference was found in total cholesterol levels between the baseline and the 3-month (P = 0.01), 12-month (P = 0.0001), 24-month (P = 0.005) and 36 months-examinations (P = 0.0001); total cholesterol levels progressively declined in group 1, and a significant difference emerged between group 1 and group 2 at 12 (P = 0.036) and 24 months (P = 0.01). Conclusions: The present study has the most numerous DTC population without DM in whom metformin has been started as off-label therapy. Metformin did not seem to have an effect on TSH. Metformin reduced total and LDL cholesterol levels, yielding a possible cardiovascular advantage. Tg data were inconclusive, perhaps because this population has a very good prognosis after primary treatments.