Mostafa A Al-Alusi1, Lin Du2, Ning Li3, Michael W Yeh4, Xuemei He5, Lewis E Braverman5, Angela M Leung6,7. 1. 1 UCLA David Geffen School of Medicine, Los Angeles, California. 2. 2 Department of Biostatistics, UCLA Fielding School of Public Health , Los Angeles, California. 3. 3 Department of Biomathematics, UCLA David Geffen School of Medicine , Los Angeles, California. 4. 4 Section of Endocrine Surgery, UCLA David Geffen School of Medicine , Los Angeles, California. 5. 5 Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine , Boston, Massachusetts. 6. 6 Division of Endocrinology, VA Greater Los Angeles Healthcare System , Los Angeles, California. 7. 7 Division of Endocrinology, UCLA David Geffen School of Medicine , Los Angeles, California.
Abstract
BACKGROUND: Levothyroxine (LT4) absorption is affected by concomitant ingestion of certain minerals, medications, and foods. It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis. This study examined the effect of metformin ingestion on LT4 absorption, as assessed by serum total thyroxine (TT4) concentrations. METHODS: A modified Food and Drug Administration LT4 bioequivalence protocol was applied to healthy, metformin-naïve, euthyroid adult volunteers. Following an overnight fast, 600 μg LT4 was administered orally. Serum TT4 concentrations were measured at baseline and at 0.5, 1, 1.5, 2, 4, and 6 h following LT4 administration. Measurements were performed before and after one week of metformin ingestion (850 mg three times daily). Peak serum TT4 concentrations, time to peak TT4 concentrations, and area under the concentration-time curve (AUC) were calculated. RESULTS: Twenty-six subjects (54% men, 27% white, age 33 ± 10 years) were studied. There were no significant differences in peak serum TT4 concentrations (p = 0.13) and time to peak TT4 concentrations (p = 0.19) before and after one week of metformin use. A trend toward reduced TT4 AUC was observed after metformin ingestion (pre-metformin 3893 ± 568 μg/dL-min, post-metformin 3765 ± 588 μg/dL-min, p = 0.09). CONCLUSIONS: LT4 absorption is unchanged by concomitant metformin ingestion. Mechanisms other than increased LT4 absorption may be responsible for the suppressed TSH concentrations observed in patients ingesting both drugs.
BACKGROUND:Levothyroxine (LT4) absorption is affected by concomitant ingestion of certain minerals, medications, and foods. It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis. This study examined the effect of metformin ingestion on LT4 absorption, as assessed by serum total thyroxine (TT4) concentrations. METHODS: A modified Food and Drug Administration LT4 bioequivalence protocol was applied to healthy, metformin-naïve, euthyroid adult volunteers. Following an overnight fast, 600 μg LT4 was administered orally. Serum TT4 concentrations were measured at baseline and at 0.5, 1, 1.5, 2, 4, and 6 h following LT4 administration. Measurements were performed before and after one week of metformin ingestion (850 mg three times daily). Peak serum TT4 concentrations, time to peak TT4 concentrations, and area under the concentration-time curve (AUC) were calculated. RESULTS: Twenty-six subjects (54% men, 27% white, age 33 ± 10 years) were studied. There were no significant differences in peak serum TT4 concentrations (p = 0.13) and time to peak TT4 concentrations (p = 0.19) before and after one week of metformin use. A trend toward reduced TT4 AUC was observed after metformin ingestion (pre-metformin 3893 ± 568 μg/dL-min, post-metformin 3765 ± 588 μg/dL-min, p = 0.09). CONCLUSIONS:LT4 absorption is unchanged by concomitant metformin ingestion. Mechanisms other than increased LT4 absorption may be responsible for the suppressed TSH concentrations observed in patients ingesting both drugs.
Authors: Nihar R Desai; William H Shrank; Michael A Fischer; Jerry Avorn; Joshua N Liberman; Sebastian Schneeweiss; Juliana Pakes; Troyen A Brennan; Niteesh K Choudhry Journal: Am J Med Date: 2012-03 Impact factor: 4.965
Authors: Franck Chiappini; Preeti Ramadoss; Kristen R Vella; Lucas L Cunha; Felix D Ye; Ronald C Stuart; Eduardo A Nillni; Anthony N Hollenberg Journal: Mol Cell Endocrinol Date: 2012-09-20 Impact factor: 4.102
Authors: Carlo Cappelli; Mario Rotondi; Ilenia Pirola; Barbara Agosti; Elena Gandossi; Umberto Valentini; Elvira De Martino; Antonio Cimino; Luca Chiovato; Enrico Agabiti-Rosei; Maurizio Castellano Journal: Diabetes Care Date: 2009-06-05 Impact factor: 19.112