title: Growth Differentiation Factor 15 as a Novel Biomarker for Metformin.
abstract: Metformin is a commonly used glucose-lowering drug. However, apart from glycemic measures, no biomarker for its presence or dose has been identified.
  
  
  
  A total of 237 biomarkers were assayed in baseline serum from 8,401 participants (2,317 receiving metformin) in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Regression models were used to identify biomarkers for metformin use.
  
  
  
  Growth differentiation factor 15 (GDF15) was strongly linked to metformin, such that the odds of metformin use per SD increase in level varied from 3.73 (95% CI 3.40, 4.09) to 3.94 (95% CI 3.59, 4.33) depending on the other included variables. For the remaining 25 linked biomarkers, the odds ranged from 0.71 to 1.24. A 1.64 ng/mL higher GDF15 level predicted a 188-mg higher metformin dose (P < 0.0001).
  
  
  
  GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada gerstein@mcmaster.ca.|Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.|Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.|Hamilton Health Sciences, Hamilton, Ontario, Canada.|Department of Pathology, McMaster University, Hamilton, Ontario, Canada.|Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.affiliation: Research and Development Diabetes, Sanofi Aventis Deutschland GmbH, Frankfurt, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Hess
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ford
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sjaarda
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kripa
authors.initials: K
authors.lastname: Raman
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: McQueen
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.|Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: ShunFu
authors.initials: S
authors.lastname: Lee
authors.affiliation: Research and Development Diabetes, Sanofi Aventis Deutschland GmbH, Frankfurt, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Haenel
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Steinberg
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006442:Glycated Hemoglobin / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000097:blood / Q000627:therapeutic use; D016015:Logistic Models; D008687:Metformin / Q000097:blood / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D055436:Growth Differentiation Factor 15; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D008687:Metformin; C526140:GDF15 protein, human