Background: Recent studies have suggested that metformin (MF) may lower thyrotropin concentration. This suggests a possible need for a dose reduction of levothyroxine in hypothyroid patients taking MF. However, contradictory results from heterogeneous study populations indicate that the underlying causes have not been completely elucidated. Patients with postoperative hypothyroidism - a condition not influenced by endogenous thyroid hormone production - have not been evaluated in order to evaluate the impact of MF. Aim: To determine the impact of MF in total thyroidectomized patients receiving levothyroxine replacement. Patients and Methods: One hundred ninety-two patients underwent total thyroidectomy during three years and were receiving levothyroxine substitution. Patients were divided into two groups depending on MF use: the non-MF group included 159 patients, of whom 134 were women [mean (SD) age, 52 (15.7) years; mean (SD) body weight, 70.2 (13.5) kg; 56 with differentiated thyroid cancer]; the MF group comprised 33 patients, of whom 24 were women [mean (SD) age, 63 (9.8) years; mean (SD) body weight, 79.3 (13.9) kg; 9 with differentiated thyroid cancer]. Levothyroxine requirements were compared between the groups, and the differentiated thyroid cancer cases were also analyzed separately. Results: Thyrotropin levels did not differ significantly between the MF and the non-MF groups. No differences in total levothyroxine dosage were found: 114 (100-150) [median (Q1-Q3)] μg in the non-MF group versus 125 (100-142) μg in the MF group (p=0.9). When calculating the weight-adjusted levothyroxine dose, significant differences were evident: 1.66 (1.38-2.08) μg/kg in the non-MF group versus 1.53 (1.26-1.70) μg/kg in the MF group (p=0.010). However, in a multivariate regression model with thyrotropin levels, age, body mass index, sex, and type of thyroid disease, MF treatment lost its significance. Conclusions: Thyroidectomized patients receiving MF treatment need a lower thyroxine dose than patients who do not receive the drug, possibly due to different characteristics (greater weight, age) of the patients with diabetes mellitus type 2. © Copyright 2013, Mary Ann Liebert, Inc. 2013.