Trial reportDiabetologia2014
Influence of TCF7L2 gene variants on the therapeutic response to the dipeptidylpeptidase-4 inhibitor linagliptin.
Trial report in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 receptor agonist, in African-American people with Type 2 diabetes: a meta-analysis of sub-population data from seven phase III trials.Diabetic medicine : a journal of the British Diabetic Association · 2017Pooled it
- Converging TCF7L2 and CDKAL1 pathways in the pathogenesis of type 2 diabetes mellitus.Acta diabetologica · 2026Review
- Precision Medicine in Type 2 Diabetes Mellitus: Utility and Limitations.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Review
- On the Verge of Precision Medicine in Diabetes.Drugs · 2022Review
- Precision Nephrology in Patients with Diabetes and Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- Awareness of Genetic Polymorphism in Drug Metabolizing Enzymes and Transporters May Promote Personalized Type 2 Diabetes Management [Response to Letter].Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Pharmacogenetics of new classes of antidiabetic drugs.Bosnian journal of basic medical sciences · 2021Review
- The Role ofDiabetes · 2021Review
- Pharmacogenetics of novel glucose-lowering drugs.Diabetologia · 2021Review
- Pharmacogenomic Studies of Current Antidiabetic Agents and Potential New Drug Targets for Precision Medicine of Diabetes.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Review
- Pharmacogenetics of Type 2 Diabetes-Progress and Prospects.International journal of molecular sciences · 2020Review
- Linagliptin and cardiorenal outcomes in Asians with type 2 diabetes mellitus and established cardiovascular and/or kidney disease: subgroup analysis of the randomized CARMELINADiabetology international · 2020Article
- Article
- Current Progress in Pharmacogenetics of Second-Line Antidiabetic Medications: Towards Precision Medicine for Type 2 Diabetes.Journal of clinical medicine · 2019Review
- Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine.Diabetes/metabolism research and reviews · 2019Review
- Precision Diabetes Is Slowly Becoming a Reality.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2019Review
- Gene x Gene Interactions Highlight the Role of Incretin Resistance for Insulin Secretion.Frontiers in endocrinology · 2019Article
- Precision diabetes: Where do we stand today?The Indian journal of medical research · 2018Article
- DPP-4 inhibitors and heart failure: a potential role for pharmacogenomics.Heart failure reviews · 2018Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIndividuals carrying variants of the transcription factor 7-like 2 gene (TCF7L2) are at increased risk for type 2 diabetes. These metabolic genetic risk factors have been linked to diminished pancreatic islet-cell responsiveness to incretins, thus pharmacological interventions aimed at amplifying endogenous incretin biology may be affected. However, clinical evidence from randomised controlled trials so far is lacking. We investigated the influence of TCF7L2 risk alleles on the response to treatment with the dipeptidylpeptidase-4 (DPP-4) inhibitor linagliptin from four 24 week, phase III, placebo-controlled trials.
methodsPharmacogenomic samples and clinical data were available from 961 patients with type 2 diabetes. Whole-blood DNA samples were genotyped for TCF7L2 single-nucleotide polymorphisms in conjunction with assessments of 24 week changes in HbA1c.
resultsLinagliptin lowered HbA1c meaningfully in all three genotypes of rs7903146 (non-risk variant carriers CC [n = 356]: -0.82% [-9.0 mmol/mol], p < 0.0001; heterozygous CT [n = 264]: -0.77% [-8.4 mmol/mol], p < 0.0001; homozygous risk variant carriers TT [n = 73]: -0.57% [-6.2 mmol/mol], p < 0.0006). No significant treatment differences were seen between CC and CT patients, although HbA1c response was reduced in TT compared with CC patients (~0.26% [~2.8 mmol/mol], p = 0.0182). CONCLUSIONS/
interpretationLinagliptin significantly improved hyperglycaemia in patients with type 2 diabetes both with and without the TCF7L2 gene diabetes risk alleles. However, differences in treatment response were observed, indicating that diabetes susceptibility genes may be an important contributor to the inter-individual variability of treatment response.
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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.