Response to metformin predicted by biomarkers

Metformin is the first-line drug used to lower blood glucose levels in people diagnosed with type 2 diabetes.

But one third of people don’t respond to metformin and five percent experience serious side effects, which is the reason many choose to stop medicating.

New researchers from Lund University in Sweden has identified biomarkers that can show in advance how patients will respond to metformin via a simple blood test.

The importance of the right treatment

Charlotte Ling, Lead Author and Professor at Lund University, said “Our study is an important step towards the goal of personalised care for people diagnosed with diabetes because it can contribute to ensuring they receive the right care as soon as they are diagnosed.”

When diet and exercise are not enough to regulate blood glucose, metformin is the first drug introduced to treat type 2 diabetes, according to international guidelines.

If it does not have the intended effect of lowering blood glucose 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 glucose levels.

Approximately 30 percent 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 Prof Ling.

One third of patients usually experience side effects such as nausea, stomach pain and diarrhoea. Five percent stop taking the medicine due to severe side effects.

Biomarkers predict the effect of medication

The study is the first pharmacoepigenetic study in diabetes, i.e. that researchers have studied how epigenetic factors, such as DNA methylation, 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 Prof Ling.

Researchers in the study 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 glucose levels) and whether or not they had suffered from side effects.

“By compiling the responses, we have found biomarkers that can identify at diagnosis which patients will benefit from and tolerate metformin.”

The study was conducted on 363 participants.  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.

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