Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study.
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Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER
Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study.
Diabetes. 2015 May;64(5):1786-93. doi: 10.2337/db14-1388. Epub 2014 Dec 15.
- PubMed ID
- 25510240 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Clopidogrel Solute carrier family 22 member 1 Protein Humans NoInhibitorDetails Codeine Solute carrier family 22 member 1 Protein Humans UnknownSubstrateInhibitorDetails Doxazosin Solute carrier family 22 member 1 Protein Humans NoInhibitorDetails Prazosin Solute carrier family 22 member 1 Protein Humans UnknownSubstrateInhibitorDetails