Study Identifies Biomarkers for Metformin Response in Patients With Diabetes


The study marks the first pharmacoepigenetic study in diabetes evaluating epigenetic factors as biomarkers to predict a drug’s effects on an individual.


Results of a new study published in Science Translational Medicine identified biomarkers, using a simple blood test, that are able to show in advance how a patient with diabetes will respond to treatment with metformin.1

Although metformin is the first-line drug that has the ability to lower blood sugar levels in individuals with type 2 diabetes, approximately 30% of all patients do not respond well to metformin and should be administered a different drug immediately, according to the study’s investigators. Adverse effects (AEs) often consist of gastrointestinal difficulties, including nausea, stomach pain, and diarrhea. An estimated 5% of patients stop taking metformin due to severe manifestations of the drug.

Investigators assessed epigenetic modifications – DNA methylations – in the blood of patients with type 2 diabetes prior to taking metformin, and followed up 1 year later to determine clinical benefit in the way of lowered blood sugar levels, as well as whether or not the individual experienced any AEs.

The study included 363 patients of 3 different cohorts of the research and quality assurance project All New Diabetics in Skåne and Uppsala, Sweden, as well as the Optimized Program of Personalized Treatment of Type 2 Diabetes (Optimed) in Latvia.

The study marks the first time that pharmacoepigenetics have been used to study diabetes. “By compiling the responses, we have found biomarkers that can identify already at diagnosis of diabetes which patients will benefit from and tolerate metformin, which will advance personalized therapy in type 2 diabetes," said the study's first author Sonia García-Calzón, PhD.2

The epigenetics-based tool may be further developed to help patients with type 2 diabetes receive optimal therapy, the investigators concluded.

Following this groundbreaking study, investigators are planning to initiate a new clinical study within a global patient cohort totaling 1000. 


  1. García-Calzón S, Perfilyev A, Martinell M, et al. Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes. Science Translational Medicine. 2020. Doi: 10.1126/scitranslmed.aaz1803
  2. Metformin for type 2 diabetes patients or not? Researchers now have the answer. News release. Lund University; September 17, 2020. Accessed September 18, 2020.
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