{"doi":"10.1161/circulationaha.123.067584","title":"Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria","abstract":"BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55-0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0-5.7), with a number needed to treat of 23 (95% CI, 18-33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event-free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1-4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4-4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0-6.7]), cardiovascular death (2.2 years [95% CI, 1.2-3.0]), and all-cause death (2.4 years [95% CI, 1.4-3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1-3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8-5.9]), and all-cause death (1.8 years [95% CI, 0.7-2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival.","journal":"Circulation","year":2023,"id":314902,"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":312,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232682,"name":"Hiddo J.L. Heerspink","orcid":"0000-0002-3126-3730","position":1,"is_corresponding":false},{"id":814150,"name":"Priya Vart","orcid":"0000-0001-5576-820X","position":2,"is_corresponding":false},{"id":28286,"name":"Brian Claggett","orcid":"0000-0002-4215-9218","position":3,"is_corresponding":false},{"id":1014566,"name":"Robert A. Fletcher","orcid":"0000-0002-0885-1788","position":4,"is_corresponding":false},{"id":300855,"name":"Clare Arnott","orcid":"0000-0001-9370-9913","position":5,"is_corresponding":false},{"id":1015521,"name":"Julianna de Oliveira Costa","orcid":null,"position":6,"is_corresponding":false},{"id":1014567,"name":"Michael O. Falster","orcid":"0000-0001-6444-7272","position":7,"is_corresponding":false},{"id":1014568,"name":"Sallie‐Anne Pearson","orcid":"0000-0001-7137-6855","position":8,"is_corresponding":false},{"id":75047,"name":"Kenneth W. Mahaffey","orcid":"0000-0002-3791-2148","position":9,"is_corresponding":false},{"id":923,"name":"Bruce Neal","orcid":"0000-0002-0490-7465","position":10,"is_corresponding":false},{"id":255772,"name":"Rajiv Agarwal","orcid":"0000-0001-8355-7100","position":11,"is_corresponding":false},{"id":6,"name":"George L. Bakris","orcid":"0000-0003-1183-1267","position":12,"is_corresponding":false},{"id":75046,"name":"Vlado Perkovic","orcid":"0000-0002-4257-7620","position":13,"is_corresponding":false},{"id":27970,"name":"Scott D. Solomon","orcid":"0000-0003-3698-9597","position":14,"is_corresponding":false},{"id":61406,"name":"Muthiah Vaduganathan","orcid":"0000-0003-0885-1953","position":15,"is_corresponding":false},{"id":300854,"name":"Brendon L. Neuen","orcid":"0000-0001-9276-8380","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:06:02.898877Z","pmid":"37952217","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":[]}