SynthesisDiabetes care2022
SGLT2 Inhibition, Choline Metabolites, and Cardiometabolic Diseases: A Mediation Mendelian Randomization Study.
Synthesis in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Association between SGLT2 inhibitors and genital cancer: a meta-analysis and mendelian randomization study.Journal of endocrinological investigation · 2026Pooled it
- Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Gout Risk: A Population-Based Comparative Cohort Study With Genetic Evidence From Mendelian Randomisation.Diabetes, obesity & metabolism · 2026Article
- Mendelian randomization analysis of the causal relationship between allergic rhinitis and depression and underlying mediation mechanisms.The World Allergy Organization journal · 2026Article
- Using human proteomic and lipidomic to exploration drug target of bladder cancer.World journal of urology · 2026Article
- Observational
- Longitudinal metabolomics reveals dynamic associations of trimethylamine N-oxide and precursors with the progression of gestational diabetes.BMC pregnancy and childbirth · 2026Article
- Plasma metabolomic profiles and risk of hip fracture among US individuals: a nested case-control and prospective cohort study.EBioMedicine · 2026Article
- Association of triglyceride glucose index with mortality in critically ill patients with atherosclerotic cardiovascular disease: analysis of the MIMIC-IV database.European journal of medical research · 2026Article
- Harnessing the gut microbiome for precision therapeutics in heart failure.Frontiers in pharmacology · 2026Review
- Mendelian Randomization Identified SLC2A9 as a Novel cis-eQTL-Mediated Susceptibility Gene in Suppressing Renal Cancer and Its Related Metabolic Mechanisms.Mediators of inflammation · 2026Article
- Trimethylamine N-Oxide Combined with Phenylacetylglutamine as Potential Biomarkers for Diabetic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Glucokinase activators contribute to gastrointestinal disease risks through metabolic-immune interplay in the gut-liver axis: insights from a multi-omics study.Acta diabetologica · 2025Article
- Gut Microbiota Influences Meningioma Pathogenesis via Circulating Metabolites: A Two-Sample Mendelian Randomization Study.Brain and behavior · 2025Article
- Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Tripeptide DT-109 (Gly-Gly-Leu) attenuates atherosclerosis and vascular calcification in nonhuman primates.Signal transduction and targeted therapy · 2025Article
- Integrated multiomics machine learning and mediated Mendelian randomization investigate the molecular subtypes and prognosis lung squamous cell carcinoma.Translational lung cancer research · 2025Article
- The Effect of SGLT2 Inhibition on Brain-related Phenotypes and Aging: A Drug Target Mendelian Randomization Study.The Journal of clinical endocrinology and metabolism · 2025Article
- SGLT-2 inhibitors are beneficial in reducing the risk of thyroid cancer: findings from a Mendelian randomization study.Acta diabetologica · 2025Article
- The Causal Mechanism Between the Dipeptidyl Peptidase-4, Heart Failure, and Other Cardiovascular Diseases: A Mendelian Randomization and Mediation Study.International journal of endocrinology · 2025Article
- Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure.JACC. Advances · 2025Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveTo investigate the causal role of choline metabolites mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in coronary artery disease (CAD) and type 2 diabetes (T2D) using Mendelian randomization (MR). RESEARCH DESIGN AND
methodsA two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on CAD and T2D; 2) causal effects of three choline metabolites, total choline, phosphatidylcholine, and glycine, on CAD and T2D; and 3) mediation effects of these metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Summary statistics for metabolites were from UK Biobank, CAD from CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) consortium, and T2D from DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the FinnGen study.
resultsSGLT2 inhibition (per 1 SD, 6.75 mmol/mol [1.09%] lowering of HbA1c) was associated with lower risk of T2D and CAD (odds ratio [OR] 0.25 [95% CI 0.12, 0.54], and 0.51 [0.28, 0.94], respectively) and positively with total choline (β 0.39 [95% CI 0.06, 0.72]), phosphatidylcholine (0.40 [0.13, 0.67]), and glycine (0.34 [0.05, 0.63]). Total choline (OR 0.78 [95% CI 0.68, 0.89]) and phosphatidylcholine (OR 0.81 [0.72, 0.91]) were associated with T2D but not with CAD, while glycine was associated with CAD (0.94 [0.91, 0.98]) but not with T2D. Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on T2D through total choline (0.91 [0.83, 0.99]) and phosphatidylcholine (0.93 [0.87, 0.99]) with a mediated proportion of 8% and 5% of the total effect, respectively, and on CAD through glycine (0.98 [0.96, 1.00]) with a mediated proportion of 2%. The results were well validated in at least one independent data set.
conclusionsOur study identified the causal roles of SGLT2 inhibition in choline metabolites. SGLT2 inhibition may influence T2D and CAD through different choline metabolites.
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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.