Projects per year
Abstract
Metformin is the most widely prescribed medication for the treatment of type 2 diabetes (T2D). However ∼25% of patients treated with metformin develop gastrointestinal (GI) side-effects leading to discontinuation of therapy in approximately 5% cases. We hypothesised 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 1915 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 to carriage of one or no deficient allele (OR=2.41, 95% CI 1.48-3.93, p < 0.001). Individuals with two reduced function OCT1 alleles who were treated with OCT1 inhibitors were over four times more likely to develop intolerance (OR=4.13, 95% CI 2.09-8.16, p < 0.001). Our results suggest that reduced OCT1 transport is an important determinant of metformin intolerance.
Original language | English |
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Pages (from-to) | 1786-1793 |
Number of pages | 8 |
Journal | Diabetes |
Volume | 64 |
Issue number | 5 |
Early online date | 15 Dec 2014 |
DOIs | |
Publication status | Published - May 2015 |
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Dive into the research topics of 'Association of organic cation transporter 1 with intolerance to metformin in Type 2 diabetes: a GoDARTS study'. Together they form a unique fingerprint.Projects
- 1 Finished
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Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)
16/02/15 → 15/08/21
Project: Research
Profiles
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Pearson, Ewan
- Population Health and Genomics - Clinical Professor (Teaching and Research) of Diabetic Medicine
Person: Academic