ArticleDiabetes care2016
Effect of Serotonin Transporter 5-HTTLPR Polymorphism on Gastrointestinal Intolerance to Metformin: A GoDARTS Study.
Article in Diabetes care, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04856683 (PRecisiOn MEdicine to Target Frailty of Endocrine-metabolic Origin), which is not on this map. Cited by 25 papers, 2 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.
PRecisiOn MEdicine to Target Frailty of Endocrine-metabolic Origin
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials.Frontiers in endocrinology · 2022Pooled it
- The Genetics of Adverse Drug Outcomes in Type 2 Diabetes: A Systematic Review.Frontiers in genetics · 2021Pooled it
- Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes.JCI insight · 2018Trial
- Article
- Article
- Prediction model for metformin intolerance in Chinese elderly patients with type 2 diabetes: derivation and external validation in a cross‑sectional study.BMC endocrine disorders · 2026Article
- The Gut Microbiota-Related Antihyperglycemic Effect of Metformin.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Metformin-Associated Gastrointestinal Adverse Events Are Reduced by Probiotics: A Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- View on Metformin: Antidiabetic and Pleiotropic Effects, Pharmacokinetics, Side Effects, and Sex-Related Differences.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.Journal of diabetes research · 2024Article
- Precision Medicine in Diabetes.Handbook of experimental pharmacology · 2023Article
- Pharmacoepigenetics in type 2 diabetes: is it clinically relevant?Diabetologia · 2022Article
- A Fat-Promoting Botanical Extract From Artemisia scoparia Exerts Geroprotective Effects on Caenorhabditis elegans Life Span and Stress Resistance.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Gut microbiota is correlated with gastrointestinal adverse events of metformin in patients with type 2 diabetes.Frontiers in endocrinology · 2022Article
- Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus.Journal of neurogastroenterology and motility · 2021Article
- A Two-Stage Study Identifies Two Novel Polymorphisms inPharmacogenomics and personalized medicine · 2021Article
- Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.The pharmacogenomics journal · 2020Article
- Mechanisms of action of metformin with special reference to cardiovascular protection.Diabetes/metabolism research and reviews · 2019Review
- Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe mechanism causing gastrointestinal intolerance to metformin treatment is unknown. We have previously shown that reduced-function alleles of organic cation transporter 1 (OCT1) are associated with increased intolerance to metformin. Considering recent findings that serotonin reuptake transporter (SERT) might also be involved in metformin intestinal absorption, and the role of serotonin in gastrointestinal physiology, in this study we investigated the association between a common polymorphism in the SERT gene and metformin gastrointestinal intolerance. RESEARCH DESIGN AND
methodsWe explored the effect of composite SERT 5-HTTLPR/rs25531 genotypes, L*L* (L
resultsThe number of low-expressing SERT S* alleles increased the odds of metformin intolerance (odds ratio [OR] 1.31 [95% CI 1.02-1.67], P = 0.031). Moreover, a multiplicative interaction between the OCT1 and SERT genotypes was observed (P = 0.003). In the analyses stratified by SERT genotype, the presence of two deficient OCT1 alleles was associated with more than a ninefold higher odds of metformin intolerance in patients carrying the L*L* genotype (OR 9.25 [95% CI 3.18-27.0], P < 10
conclusionsOur results indicate that the interaction between OCT1 and SERT genes might play an important role in metformin intolerance. Further studies are needed to replicate these findings and to substantiate the hypothesis that metformin gastrointestinal side effects could be related to the reduced intestinal serotonin uptake.
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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 OpenQuestion graph.