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

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.