Novel nonglycemic biomarker for metformin

The Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial delivers more insight on biomarkers that have potential to help treat patients with dysglycemia.1 Hertzel C. Gerstein and colleagues report Growth Differentiation Factor 15 (GDF15) as a novel biomarker for the use and dosing of metformin, in a study published in Diabetes Care last month.

Metformin is an oral diabetes medication that is used to treat high blood sugar levels in people with type 2 diabetes.  The research shows that GDF15 levels are not only a nonglycemic biomarker for the use of metformin but its concentration also reflects the dose of metformin.

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).

Researchers utilized Multi-Analyte Profiling (MAP) to analyzed 237 biomarkers in baseline serum from 8,401 ORIGIN trial participants, 28% of which were receiving various doses of metformin. Along with these findings from this ORIGIN trial regression analysis, the use of Myriad RBM’s DiscoveryMAP platform was also used to identify a pattern of biomarkers that may help predict cardiovascular events in patients with type II diabetes when paired with clinical risk factors.2  GDF15 was one of 15 biomarkers included in this pattern.


Want to learn more? View Dr. Gerstein’s presentation from EASD 2016, Performance of the validated ORIGIN cardiovascular biomarker panel in HOPE study participants with diabetes.



1. Growth Differentiation Factor 15 as a Novel Biomarker for Metformin
Hertzel C. Gerstein, Guillaume Pare, Sibylle Hess, Rebecca J. Ford, Jennifer Sjaarda, Kripa Raman, Matthew McQueen, ShunFu Lee, Heinz Haenel, Gregory R. Steinberg, for the ORIGIN Investigators
Diabetes Care 2016 Dec; dc161682.

2. Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Hertzel C. Gerstein, Guillaume Paré, Matthew J. McQueen, Heinz Haenel, Shun Fu Lee, Janice Pogue, Aldo P. Maggioni, Salim Yusuf, Sibylle Hess
and for the Outcome Reduction With Initial Glargine Intervention Trial Investigators
Circulation. 2015;132:2297-2304.