2020_09_25_FAR_Garcia_calzon

European researchers have found epigenetic markers that determine the response of patients with diabetes subject 2 to metformin, the most widely used drug to treat the disease. This is DNA methylation, which is already used in the treatment of other diseases such as cancer to predict the effect of a given drug. This study is an important milestone on the road to personalized medicine in diabetes, since it makes it possible to guarantee with a simple blood test that the patient will receive the appropriate pharmacological treatment as soon as a diagnosis is made.

"Every year around the world, metformin is prescribed to approximately 150 million diabetics and 30% of them do not respond to treatment, which can lead to cardiovascular complications and increased mortality and morbidity in a short period of time. In addition, 5% stop taking the drug due to the presence of severe adverse effects," explains Sonia García-Calzón, professor and researcher at School of Pharmacy and Nutrition at the University of Navarra, and first author of work, which has just been published in the American journal ScienceTranslational Medicine.

Charlotte Ling, professor at Lund University (Sweden) and head of the study, adds: "If the patient takes a long time to receive the correct treatment, there is a risk of complications due to high blood sugar levels. Therefore, those who do not respond to metformin should be given another drug from the start, so it is important to be able to identify these cases as early as possible."

Towards precision pharmacology

This is the first pharmacoepigenetic study applied to diabetes, which analyzes factors such as DNA methylation to determine therapeutic success. García-Calzón explains that "until now, this method has been used in the treatment of cancer, but never before had it been applied to diabetes".

To do this, the researchers analyzed epigenetic modifications (so-called DNA methylations, marks that regulate gene expression) in the blood of people diagnosed with diabetes before they started taking metformin.After a year of follow-up, they were able to see which patients had benefited from the treatment (with a consequent decrease in blood sugar levels) and whether or not they had suffered side effects.

"By compiling the responses, we have found markers that can be identified at the time of diabetes diagnosis and know which patients will benefit from and tolerate metformin. In this way, we can advance personalized therapy for diabetes subject 2," says García-Calzón.

The study was conducted in 363 participants from three different patient cohorts from Sweden and Latvia. The next step will be a new clinical study with a significantly larger group of patients, around 1,000, from different parts of the world.