Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes: A nested, case–control study

Research output: Contribution to journalArticle


Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed 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 participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.


External organisations
  • University of Pisa
  • University of Exeter
  • University of Dundee
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems


  • cardiovascular disease, GDF-15, growth differentiation factor-15, metformin, type 2 diabetes
Original languageEnglish
Pages (from-to)412-416
JournalDiabetes, Obesity and Metabolism
Issue number2
Early online date2018 Sep 3
Publication statusPublished - 2019 Feb
Publication categoryResearch