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Diabetologia. 2017 Sep;60(9):1648-1655. doi: 10.1007/s00125-017-4335-y. Epub 2017 Aug 3.

The pharmacogenetics of metformin.

Florez JC1,2,3,4,5.

Author information

1
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. jcflorez@partners.org.
2
Center for Genomic Medicine, Simches Research Building-CPZN 5.250, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA. jcflorez@partners.org.
3
Metabolism Program, Broad Institute, Cambridge, MA, USA. jcflorez@partners.org.
4
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. jcflorez@partners.org.
5
Department of Medicine, Harvard Medical School, Boston, MA, USA. jcflorez@partners.org.

Abstract

Despite its widespread use as the first-line agent for the treatment of type 2 diabetes, it has become clear that metformin does not work optimally for everyone. Elucidating who are the likely metformin responders and non-responders is hampered by our limited knowledge of its precise molecular mechanism of action. One approach to achieve the related goals of stratifying patients into response subgroups and identifying the molecular targets of metformin involves the deployment of agnostic genome-wide approaches in cohorts of appropriate size to attain sufficient statistical power. While candidate gene studies have shed some light on the role of genetic variation in influencing metformin response, genome-wide association studies are beginning to provide additional insight that is unconstrained by prior knowledge. To fully realise their potential, much larger samples need to be assembled via international collaboration, preferably involving the academic community, government and the pharmaceutical industry.

KEYWORDS:

Genome-wide association studies; Metformin; Pharmacogenetics; Review; Single nucleotide polymorphisms; Type 2 diabetes

PMID:
28770331
PMCID:
PMC5709222
DOI:
10.1007/s00125-017-4335-y
[Indexed for MEDLINE]
Free PMC Article

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