title: Metformin Does Not Suppress Serum Thyrotropin by Increasing Levothyroxine Absorption.
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.
authors.affiliation: 1 UCLA David Geffen School of Medicine, Los Angeles, California.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Al-Alusi
authors.affiliation: 2 Department of Biostatistics, UCLA Fielding School of Public Health , Los Angeles, California.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.affiliation: 3 Department of Biomathematics, UCLA David Geffen School of Medicine , Los Angeles, California.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: 4 Section of Endocrine Surgery, UCLA David Geffen School of Medicine , Los Angeles, California.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Yeh
authors.affiliation: 5 Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Xuemei
authors.initials: X
authors.lastname: He
authors.affiliation: 5 Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine , Boston, Massachusetts.
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Braverman
authors.affiliation: 6 Division of Endocrinology, VA Greater Los Angeles Healthcare System , Los Angeles, California.|7 Division of Endocrinology, UCLA David Geffen School of Medicine , Los Angeles, California.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Leung
mesh_terms: D000328:Adult; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D013972:Thyrotropin; D008687:Metformin; D013974:Thyroxine