Growth Differentiation Factor 15 as a Novel Biomarker for Metformin

Diabetes Care. 2017 Feb;40(2):280-283. doi: 10.2337/dc16-1682. Epub 2016 Dec 14.

Abstract

Objective: Metformin is a commonly used glucose-lowering drug. However, apart from glycemic measures, no biomarker for its presence or dose has been identified.

Research design and methods: 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.

Results: 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).

Conclusions: GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.

Trial registration: ClinicalTrials.gov NCT00069784.

MeSH terms

  • Biomarkers / blood*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dose-Response Relationship, Drug
  • Glycated Hemoglobin / metabolism
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Glargine / blood
  • Insulin Glargine / therapeutic use
  • Logistic Models
  • Metformin / blood
  • Metformin / therapeutic use*
  • Polymorphism, Single Nucleotide

Substances

  • Biomarkers
  • Blood Glucose
  • GDF15 protein, human
  • Glycated Hemoglobin A
  • Growth Differentiation Factor 15
  • Hypoglycemic Agents
  • Insulin Glargine
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00069784