“Our study constitutes an important step towards the goal of personalised care for diabetes patients because it can contribute to ensuring that the right person receives the right care as soon as there is a diagnosis”, says Charlotte Ling, professor of epigenetics at Lund University, who led the study.
When diet and exercise are not enough to regulate blood sugar, metformin is the first drug introduced to treat type 2 diabetes, according to international guidelines. If it does not have the intended effect in the form of lowered blood sugar levels, or if the patient experiences serious side effects, patients then go on to trial other drugs.
“If it takes a long time for the patient to receive the correct treatment, there is a risk of complications due to the elevated blood sugar levels. Approximately 30 per cent of all patients with type 2 diabetes do not respond to metformin and should be given another drug right from the start. For this reason, it is important to be able to identify these patients upon diagnosis”, says Charlotte Ling.
One third of patients experience side effects usually in the form of gastrointestinal difficulties such as nausea, stomach pain and diarrhoea. Five per cent stop taking the medicine due to severe side effects.
The study is the first pharmacoepigenetic study in diabetes, i.e. that researchers have studied how epigenetic factors, such as DNA methylation (see fact box), can be used as biomarkers to predict the effect of a drug.
“To a certain extent, pharmacoepigenetics has been used within cancer care to predict how a person will respond to a treatment, however, it has never been done in diabetes care before”, says Charlotte Ling.
Researchers in the study have looked at epigenetic modifications, so-called DNA methylations, in blood from individuals diagnosed with diabetes before they started taking metformin. In a follow-up a year later, the researchers could see which patients had benefited from the treatment (with resulting lowered blood sugar levels) and whether or not they had suffered from side effects.
“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 personalised therapy in type 2 diabetes”, says the study’s first author Sonia García-Calzón.
The study was conducted on 363 participants from three different patient cohorts (All New Diabetics in Skåne, All New Diabetics in Uppsala and Optimed from Latvia). As a next step, the researchers are planning for a new clinical study in which they will repeat the study with a larger patient group – 1000 patients will be invited to participate from all around the world.
The study was financed with support from: the Novo Nordisk Foundation, the Swedish Research Council, Region Skåne (ALF), H2020-Marie Skłodowska-Curie grant agreement no. 706081(EpiHope), ERC Consolidator Grant, the Swedish Heart-Lung Foundation, EFSD, EXODIAB, the Swedish Foundation for Strategic Research, the Swedish Diabetes Foundation and the Albert Påhlsson Foundation.
Charlotte Ling, professor of epigenetics at the Lund University Diabetes Centre
charlotte [dot] ling [at] med [dot] lu [dot] se
Publication in Science Translational Medicine: Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes