title: Does metformin have a "buffer effect" on serum TSH levels in euthyroid diabetic patients?
abstract: OBJECTIVE
  In the last few years a number of studies have found that metformin has a thyrotropin (TSH)-lowering effect in patients with type 2 diabetes (DM2) and that this effect disappears after discontinuation of the drug. Initial studies were carried out in hypothyroid patients on levothyroxine (LT4) treatment. However, this effect was observed only when serum TSH levels were elevated. The aim of this study was to assess the effect of metformin treatment on serum TSH levels in euthyroid DM2 patients.
  
  
  METHODS
  A retrospective study was conducted in seven primary health care centers in Spain. The study included 278 DM2 patients (110 females). Serum TSH level was tested before and one year after the onset of metformin treatment. We compared both TSH levels by paired t-tests. The sample was divided into four hierarchical clusters (C1 to C4), according to the Euclidean distance of the initial TSH level. No patient received LT4 treatment.
  
  
  RESULTS
  Pre-metformin serum TSH level (2.00 ± 0.76 mU/L) was statistically significantly lower than post-metformin level (2.20 ± 0.87 mU/L; P <0.001). Interestingly, this trend was observed only in clusters 1 and 2 (those with lower baseline TSH levels), whereas the trend was lost in clusters 3 and 4. The difference between pre- and post-metformin TSH levels follows a mathematical model. According to this model, the TSH threshold point level is 3.00 mU/L.
  
  
  CONCLUSIONS
  Metformin seems to induce a "buffer effect" on TSH secretion in euthyroid diabetic individuals. Hence, our study found an unreported TSH behavior after metformin treatment.
authors.affiliation: Department of Endocrinology and Nutrition, Clίnica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Santos-Palacios
authors.affiliation: Department of Health Sciences, Public University of Navarra, Pamplona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Brugos-Larumbe
authors.affiliation: Department of Preventive Medicine, Clίnica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Guillén-Grima
authors.affiliation: Department of General Surgery, Spital Zollikerberg, Zrich, Switzerland.
authors.forename: Ane
authors.initials: A
authors.lastname: Garmendia-Madariaga
authors.affiliation: Department of Endocrinology and Nutrition, Clίnica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Galofré
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013972:Thyrotropin / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D013972:Thyrotropin; D008687:Metformin