Genetic variants could explain different responses to metformin

A large international study reports that genetic difference among patients could explain why some respond better to metformin than others.
Metformin, a type 2 diabetes drug, is a first-line treatment for the condition which works to lower blood sugar levels in the body.
This new research from the Metformin Genetics Consortium, which involved scientists from Scotland the US, evaluated 13,123 metformin-treated participants in a three-stage genome-wide association study.
The first phase involved 1,373 patients from Tayside, Scotland; the second phase replicated the first phase in a cohort of 1,223 patients of European ancestry from Scotland; and the third phase involved 6,488 participants of European ancestry and 2,566 of non-European ancestry.
Kathy Giacomini, PhD, UC San Francisco’s schools of Pharmacy and Medicine, and Ewan Pearso, PhD, University of Dundee in Scotland, found that a common variant of the gene SLC2A2 was correlated with a strong response to metformin.
The SLC2A2 gene encodes GLUT2, a glucose transporter protein, but people with a variant of the gene have a reduced ability to manage blood glucose levels. Because metformin slows the production of glucose by liver, the drug could be able to reverse the effects of this variant.
Furthermore, the researchers uncovered that overweight people who carry two copies of the SLC2A2 variant responded much better to metformin, equivalent to receiving an extra 550mg.
These findings suggest that the biological causes of high blood sugar could vary, and demonstrate how a patient’s genetics can determine the efficacy of a drug, according to Pearson.
“We need to undertake further clinical studies before we can change the way we use metformin, but this finding suggests that some patients should be treated with higher doses than others to achieve the same effect,” said Pearson.
“This really does move us a step closer to truly targeted therapy in the treatment of diabetes.”
The Metformin Genetics Consortium now plans to investigate how ethnicity affects metformin responses and side effects that can lead to discontinuation of the drug.
The findings appear in the online journal Nature.