Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study.

Abstract:

:Metformin is the most widely prescribed medication for the treatment of type 2 diabetes (T2D). However, gastrointestinal (GI) side effects develop in ~25% of patients treated with metformin, leading to the discontinuation of therapy in ~5% of cases. We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation. We compared the phenotype, carriage of reduced-function OCT1 variants, and concomitant prescribing of drugs known to inhibit OCT1 transport in 251 intolerant and 1,915 fully metformin-tolerant T2D patients. We showed that women and older people were more likely to be intolerant to metformin. Concomitant use of medications, known to inhibit OCT1 activity, was associated with intolerance (odds ratio [OR] 1.63 [95% CI 1.22-2.17], P = 0.001) as was carriage of two reduced-function OCT1 alleles compared with carriage of one or no deficient allele (OR 2.41 [95% CI 1.48-3.93], P < 0.001). Intolerance was over four times more likely to develop (OR 4.13 [95% CI 2.09-8.16], P < 0.001) in individuals with two reduced-function OCT1 alleles who were treated with OCT1 inhibitors. Our results suggest that reduced OCT1 transport is an important determinant of metformin intolerance.

journal_name

Diabetes

journal_title

Diabetes

authors

Dujic T,Zhou K,Donnelly LA,Tavendale R,Palmer CN,Pearson ER

doi

10.2337/db14-1388

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1786-93

issue

5

eissn

0012-1797

issn

1939-327X

pii

db14-1388

journal_volume

64

pub_type

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