Observational studyDiabetic medicine : a journal of the British Diabetic Association2016
Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes.
Observational study in Diabetic medicine : a journal of the British Diabetic Association, 2016. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports an association that does not count as treatment evidence, such as OR 2.31 (1.07 to 5.01) for adverse events & safety. Cited by 62 papers, 3 of them syntheses that pooled it.
What it found
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Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034).
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Metformin×adverse events & safety
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 3 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis.Frontiers in public health · 2023Pooled it
- The Genetics of Adverse Drug Outcomes in Type 2 Diabetes: A Systematic Review.Frontiers in genetics · 2021Pooled it
- Pooled it
- Trial
- Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.PloS one · 2018Trial
- Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015-2025).Diseases (Basel, Switzerland) · 2026Review
- Transcutaneous auricular vagus nerve stimulation to alleviate metformin-associated gastrointestinal adverse events and optimize glycaemic control: a randomized, sham-controlled pilot trial protocol.Frontiers in neuroscience · 2026Article
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Transporter gene variants influencing metformin pharmacokinetics and pharmacodynamics common in European populations: a pharmacogenetic narrative review.Frontiers in pharmacology · 2026Review
- Pharmacogenetics and Molecular Ancestry ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Genetic Variants ofGenes · 2025Article
- Metformin efficacy and tolerance according to genetic polymorphisms of organic cation transporter 1 in Tunisian patients with type 2 diabetes.Frontiers in endocrinology · 2025Article
- Impact ofJournal of diabetes and metabolic disorders · 2024Article
- Impact ofBiomedical reports · 2024Article
- Longitudinal assessment of SNPs rs72552763 and rs622342 inFrontiers in pharmacology · 2024Article
- Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus.Pharmacogenomics and personalized medicine · 2024Article
- Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes.Research in pharmaceutical sciences · 2023Article
- Assessing the multitargeted antidiabetic potential of three pomegranate peel-specific metabolites: An in silico and pharmacokinetics study.Food science & nutrition · 2023Article
- Structural basis of promiscuous substrate transport by Organic Cation Transporter 1.Nature communications · 2023Article
- Versatile Solid Modifications of Multicomponent Pharmaceutical Salts: Novel Metformin-Rhein Salts Based on Advantage Complementary Strategy Design.Pharmaceutics · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
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aimsMetformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20-30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes.
methodsThis prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression.
resultsForty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034).
conclusionsIn conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.