Metformin is the key factor for elevated plasma GDF-15 levels in type 2 diabetes: a nested, case-control study

SUMMIT Consortium, Andrea Natali (Lead / Corresponding author), Lorenzo Nesti, Elena Venturi, Angela C. Shore, Faisel Khan, Kim Gooding, Phillip E. Gates, Helen C. Looker, Fiona Dove, Isabel Goncalves, Margaretha Persson, Jan Nilsson

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Produced as a tissue defence-response to hypoxia and inflammation, Growth Differentiation Factor-15 (GDF-15) is raised in subjects on metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analyzed the data of the SUMMIT cohort (n=1,438), a 4 centres, nested, case-control study aiming at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in subjects with and without diabetes were age, plasma creatinine, NT-proBNP, diuretic use, smoke load, and HbA1c . In subjects with diabetes metformin treatment was associated to a 40% rise in GDF-15, which was independent to the other major factors largely explaining their elevated GDF-15 levels. The relatively higher GDF-15 bioavailability might contribute to explain the protective cardiovascular effects of metformin. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)412-416
Number of pages5
JournalDiabetes, Obesity & Metabolism
Issue number2
Early online date3 Sept 2018
Publication statusPublished - 10 Jan 2019


  • GDF-15
  • cardiovascular disease
  • growth differentiation factor-15
  • metformin
  • type 2 diabetes
  • Diabetes Mellitus, Type 2/blood
  • Growth Differentiation Factor 15/blood
  • Humans
  • Middle Aged
  • Risk Factors
  • Male
  • Cardiovascular Diseases/blood
  • Case-Control Studies
  • Metformin/therapeutic use
  • Aged, 80 and over
  • Adult
  • Biomarkers/blood
  • Female
  • Aged
  • Diabetic Angiopathies/blood
  • Cohort Studies

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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