{"doi":"10.2337/dc22-0866","title":"Interleukin-6 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS","abstract":"OBJECTIVE: The 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 METHODS: Patients 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. RESULTS: The 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. CONCLUSIONS: In 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.","journal":"Diabetes Care","year":2022,"id":237845,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":860768,"name":"Meir Schechter","orcid":"0000-0002-5071-3143","position":1,"is_corresponding":false},{"id":666139,"name":"Taha Sen","orcid":"0000-0001-6359-2945","position":2,"is_corresponding":false},{"id":814150,"name":"Priya Vart","orcid":"0000-0001-5576-820X","position":3,"is_corresponding":false},{"id":300854,"name":"Brendon L. Neuen","orcid":"0000-0001-9276-8380","position":4,"is_corresponding":false},{"id":923,"name":"Bruce Neal","orcid":"0000-0002-0490-7465","position":5,"is_corresponding":false},{"id":300855,"name":"Clare Arnott","orcid":"0000-0001-9370-9913","position":6,"is_corresponding":false},{"id":75046,"name":"Vlado Perkovic","orcid":"0000-0002-4257-7620","position":7,"is_corresponding":false},{"id":21979,"name":"Paul M. Ridker","orcid":"0000-0003-1249-4522","position":8,"is_corresponding":false},{"id":231214,"name":"Katherine R. Tuttle","orcid":"0000-0002-2235-0103","position":9,"is_corresponding":false},{"id":660509,"name":"Michael K. Hansen","orcid":"0000-0002-0062-0520","position":10,"is_corresponding":false},{"id":232682,"name":"Hiddo J.L. Heerspink","orcid":"0000-0002-3126-3730","position":11,"is_corresponding":false},{"id":860767,"name":"Akihiko Koshino","orcid":"0000-0002-9432-2427","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:22:21.693802Z","pmid":"36134918","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}