Growth Differentiation Factor 15 as a Novel Biomarker for Metformin
Abstract
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.
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In the ORIGIN trial, GDF15 was identified as a biomarker linked to positive cardiovascular outcomes and also elevated in those patients receiving metformin.
“As a result of an analysis of data from the ORIGIN trial (Outcome Reduction with Initial Glargine Intervention), GDF15 was identified as a biomarker linked to positive CV outcomes and also elevated in those patients receiving metformin (80, 81).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [81]
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References 14 · Cited by 169
- Authors
- Gerstein, H. C., Pare, G., Hess, S., Ford, R. J., Sjaarda, J., Raman, K., McQueen, M., Lee, S., Haenel, H., & Steinberg, G. R.
- Affiliations
- Population Health Research Institute (CA)
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
- Sanofi (Germany) (DE)
- McMaster University (CA)
- Corresponding author
- Gerstein, Hertzel C.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2016-12-14
- Volume
- 40
- Issue
- 2
- Pages
- 280-283
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2561702225
- Cited by
- 169
- References
- 14
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 30 · 2023: 25 · 2022: 22 · 2021: 19 · 2020: 21 · 2019: 14 · 2018: 8 · 2017: 2
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sanofi
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- growth differentiation factor 15, GDF15, metformin, metformin dose, dysglycemia, serum biomarkers, ORIGIN trial, antidiabetic drugs
- MeSH terms
- Insulin Glargine, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Metformin, Biomarkers, Logistic Models, Polymorphism, Single Nucleotide, Growth Differentiation Factor 15
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