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.