ArticleDiabetes2009
Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02783469 (Genetics of Diabetes Audit and Research in Tayside Scotland), which is not on this map. Cited by 90 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Genetics of Diabetes Audit and Research in Tayside Scotland (DOLORisk Dundee)
Who cites it
90 citing papers in PubMed, 5 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Influence of Solute Carrier Family 22 Member 1 (Current diabetes reviews · 2024Pooled it
- 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
- Pooled it
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- The pharmacogenetics of type 2 diabetes: a systematic review.Diabetes care · 2014Pooled it
- Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes.Diabetologia · 2019Trial
- Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial.Diabetologia · 2015Trial
- Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.Diabetes · 2010 · on this mapTrial
- Context-Dependent Modulation of Ferroptosis by Metformin: Mechanisms, Therapeutic Implications and Open Questions.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Reframing metformin as a gut-targeted glucose-lowering therapy: Mechanistic insights and translational relevance.Molecular metabolism · 2025Article
- Article
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 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
- Understanding the action mechanisms of metformin in the gastrointestinal tract.Frontiers in pharmacology · 2024Review
- Longitudinal assessment of SNPs rs72552763 and rs622342 inFrontiers in pharmacology · 2024Article
- Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.Journal of diabetes research · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveMetformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose. We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND
methodsThe Diabetes Audit and Research in Tayside Scotland (DARTS) database includes prescribing and biochemistry information and clinical phenotypes of all patients with diabetes within Tayside, Scotland, from 1992 onwards. R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin. We assessed metformin response by modeling the maximum A1C reduction in 18 months after starting metformin and investigated whether a treatment target of A1C <7% was achieved. Sustained metformin effect on A1C between 6 and 42 months was also assessed, as was the time to metformin monotherapy failure. Covariates were SLC22A1 genotype, BMI, average drug dose, adherence, and creatinine clearance.
resultsA total of 1,531 patients were identified with a definable metformin response. R61C and 420del variants did not affect the initial A1C reduction (P = 0.47 and P = 0.92, respectively), the chance of achieving a treatment target (P = 0.83 and P = 0.36), the average A1C on monotherapy up to 42 months (P = 0.44 and P = 0.75), or the hazard of monotherapy failure (P = 0.85 and P = 0.56).
conclusionsThe SLC22A1 loss-of-function variants, R61C and 420del, do not attenuate the A1C reduction achieved by metformin in patients with type 2 diabetes.
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Registered trials
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 Socratic graph.