Trial reportDiabetes care2022
Interleukin-6 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS.
Trial report in Diabetes care, 2022. The graph read 2 numbers from its abstract, feeding 1 cell of the map: it favours the comparator in 1. Cited by 38 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
Over 6 years, IL-6 increased by 5.8% (95% CI 3.4, 8.3) in the placebo group.
Canagliflozin modestly attenuated the IL-6 increase (absolute percentage difference vs. placebo 4.4% [95% CI 1.3, 9.9; P = 0.01]).
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
SGLT2 inhibitors×inflammation & biomarkers
ContradictsOpen on the map →What to test next →5 readable studies in this cell: 2 favour the treatment, 2 find no difference, 1 favour the comparator.
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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Impact of DPP-4 Inhibitors on Interleukin Levels in Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials.BMC endocrine disorders · 2023Pooled it
- Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial.Cardiovascular diabetology · 2023 · on this mapTrial
- Targeting Interleukin-6 for Treatment of CKD and Cardiovascular Disease.Kidney international reports · 2026Review
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- Investigation of Biomarker Response to SGLT2 Inhibition in Heart Failure (SiN-HF).Cardiovascular drugs and therapy · 2026Article
- The AGE-RAGE-DIAPH1 Axis in Type 2 Diabetes and Metabolic Dysfunction: From Carbonyl Stress to Diabetic Myocardial and Neuronal Injury.International journal of molecular sciences · 2026Review
- Impact of herpes zoster and post-zoster SGLT2 inhibitors initiation on cardiorenal outcomes in type 2 diabetes mellitus.BMC endocrine disorders · 2026Article
- Association of periodontitis with reduced kidney function and albuminuria in early chronic kidney disease: a population-based study.International journal of oral science · 2026Article
- Triglyceride-Rich Lipoproteins and Inflammation: Independent and Synergistic Roles in Cardiovascular Disease.Current atherosclerosis reports · 2026Review
- IL-6 and lL-17 as potential biomarkers for premature coronary artery disease: a cross-sectional study.BMC cardiovascular disorders · 2026Article
- A Review of Emerging Biomarkers Connecting Diabetes and Ischemic Stroke: Implications for Early Detection and Risk Stratification.Journal of diabetes research · 2026Review
- Chronic inflammation is not associated with attenuated sodium-glucose co-transporter 2 inhibitor-induced hemoglobin increase in patients with diabetes.Journal of diabetes investigation · 2026Article
- Mechanisms of diabetic kidney disease and established and emerging treatments.Nature reviews. Endocrinology · 2026Review
- Can Clinical Biomarkers Guide Optimal Therapeutic Selection in Type 2 Diabetes Mellitus? A Scoping Review.Current atherosclerosis reports · 2025Article
- Sodium-glucose cotransporter 2 inhibitors for hypertension in cardiovascular-kidney-metabolic syndrome.Experimental physiology · 2025Review
- Nicotinamide mononucleotide protects against diabetic nephropathyWorld journal of diabetes · 2025Article
- Immune Dysregulation Connecting Type 2 Diabetes and Cardiovascular Complications.Life (Basel, Switzerland) · 2025Review
- Impact of sodium-glucose transport protein-2 (SGLT2) inhibitors on the inflammasome pathway in acute myocardial infarction in type 2 diabetes mellitus: a comprehensive review.Cardiovascular diabetology · 2025Review
- Chronic kidney disease enhances alternative pathway activity: a new paradigm.The Journal of clinical investigation · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
objectiveThe inflammatory cytokine interleukin-6 (IL-6) is associated with cardiovascular (CV) and kidney outcomes in various populations. However, data in patients with type 2 diabetes are limited. We assessed the association of IL-6 with CV and kidney outcomes in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and determined the effect of canagliflozin on IL-6. RESEARCH DESIGN AND
methodsPatients with type 2 diabetes at high CV risk were randomly assigned to canagliflozin or placebo. Plasma IL-6 was measured at baseline and years 1, 3, and 6. The composite CV outcome was nonfatal myocardial infarction, nonfatal stroke, or CV death; the composite kidney outcome was sustained ≥40% estimated glomerular filtration rate decline, end-stage kidney disease, or kidney-related death. Multivariable-adjusted Cox proportional hazards regression was used to estimate the associations between IL-6 and the outcomes. The effect of canagliflozin on IL-6 over time was assessed with a repeated-measures mixed-effects model.
resultsThe geometric mean IL-6 at baseline, available in 3,503 (80.2%) participants, was 1.7 pg/mL. Each doubling of baseline IL-6 was associated with 14% (95% CI 4, 24) and 21% (95% CI 1, 45) increased risk of CV and kidney outcomes, respectively. Over 6 years, IL-6 increased by 5.8% (95% CI 3.4, 8.3) in the placebo group. Canagliflozin modestly attenuated the IL-6 increase (absolute percentage difference vs. placebo 4.4% [95% CI 1.3, 9.9; P = 0.01]). At year 1, each 25% lower level of IL-6 compared with baseline was associated with 7% (95% CI 1, 22) and 14% (95% CI 5, 22) lower risks for the CV and kidney outcome, respectively.
conclusionsIn patients with type 2 diabetes at high CV risk, baseline IL-6 and its 1-year change were associated with CV and kidney outcomes. The effect of IL-6-lowering therapy on CV, kidney, and safety outcomes remains to be tested.
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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 Socratic graph.