{"publication_id":"89c570cf-7f20-49de-a349-6ab8241f2855","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 10/12 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on SGLT2 inhibitor across 12 included source papers and 692 high-confidence extracted claims.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_3","claim":"The evidence profile contains 2 direct clinical sources, 10 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 21 cross-study disagreements across the evidence base.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_4","claim":"Positive study-level signals are summarized in the safety outcome class; null signals are not the dominant direction in any outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the contextual adjacent evidence, cardiometabolic, safety and comorbidity, and longevity outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_5","claim":"The conclusion is that SGLT2 inhibitor should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_6","claim":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_7","claim":"Aging populations are reshaping the clinical priorities of internal medicine and cardiology alike, and the question of whether drugs already in widespread use can extend healthspan — the years a person spends free of chronic-disease disability — has moved from speculative to operational. SGLT2 inhibitors sit at the intersection of two converging pressures: a demographic transition in which multimorbid adults now live long enough to accumulate heart failure, chronic kidney disease, and frailty, and a regulatory environment that has, over the past decade, granted these agents expanding labels across diabetes, heart failure, and renal disease. The question of whether SGLT2 inhibitors meaningfully slow aging biology — rather than simply attenuate single-organ decline — is no longer hypothetical, because mechanistic and real-world signals continue to accumulate faster than the trial apparatus can test them. Frailty is itself a powerful adverse prognostic marker in cardiovascular and renal medicine, with gait-speed thresholds near 0.8 m/s (Studenski 2011) and 0.6 m/s (Cesari 2009) widely used to stratify risk, and grip-strength cutoffs of 27 kg for men and 16 kg for women (Cruz-Jentoft 2019) anchoring sarcopenia diagnosis. The field therefore needs to know whether SGLT2 inhibitors do anything to the trajectory underlying these markers, not only to the discrete events used in registrational trials. Why this question matters now is that a single mechanistic reframing could change prescribing for tens of millions of adults, making the evidentiary stakes unusually high relative to the incremental cost of producing the synthesis itself.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_8","claim":"The background evidence for SGLT2 inhibitor is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Nassif 2021, Spertus 2022 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_9","claim":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_10","claim":"Across the retained sources, positive signals cluster around the contextual adjacent evidence and safety outcome classes; null signals around the cardiometabolic, contextual adjacent evidence, safety and comorbidity outcome classes; and negative or adverse signals around the contextual adjacent evidence outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_11","claim":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_12","claim":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_13","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_14","claim":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_15","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, longevity, safety, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_16","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_17","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_18","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_19","claim":"| SGLT2 inhibitor / Contextual Adjacent Evidence | n=6; claims=451 | significant source statistic in 4/6 sources; receipt-level direction coded unclear | 2 direct; 3 indirect; 1 review | limited corpus depth in this outcome class |","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_20","claim":"Contextual Adjacent Evidence: n=6; claims=451; mixed signal in 3/6 sources | directness: 2 direct; 3 indirect; 1 review; main limitation: directionally heterogeneous.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_21","claim":"Two curated references define the cardiometabolic evidence base for SGLT2, anchored to type 2 diabetes and chronic heart failure populations. Zhang 2022 is an observational cohort synthesis (canonical trial registration NCT01064414) reviewing finerenone versus SGLT2 inhibitors on new-onset atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease. Metabolism to Microcirculation the Multifaceted 2026 is a systematic review or meta-analysis cataloguing the vascular benefits of SGLT2 inhibitors in chronic heart failure, including dapagliflozin's effects on endothelial cell energy metabolism in cell cultures and mouse models. Endpoint reporting in this outcome class is therefore anchored to registry-level observational synthesis rather than to a single within-source primary RCT endpoint table.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_22","claim":"In animal/preclinical evidence, for the Metabolism to Microcirculation the Multifaceted 2026 systematic review, the source records directness as review and effect direction as unclear, with p values left empty; consequently, no within-source summary estimate is restated in prose. The numeric density in this subsection is therefore modest, and the evidence synthesis should be consulted for the exact effect-direction mapping per reference.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_23","claim":"Within-corpus tensions in this outcome class arise from the mismatch in study design and in effect-direction reporting rather than from discrepant point estimates. The picked thesis notes that null findings dominate the cardiometabolic class; consistent with that framing, the only within-source quantitative effect (RR 0.79 for finerenone versus SGLT2 inhibitors on atrial fibrillation) is reported in an observational cohort with empty p values, and the systematic review records no direction. Future human RCTs in chronic heart failure with adjudicated cardiometabolic endpoints will be needed to sharpen these signals.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_24","claim":"In the clinical RCT stratum, Nassif 2021 reported multiple dapagliflozin-versus-placebo comparisons in HFpEF adults, with reported p-values of P = 0.001, P = 0.003, P = 0.026, P = 0.007, P = 0.009, P = 0.03, P = 0.046, P = 0.06, and P = 0.01 across the trial's primary and secondary endpoints, and an effect direction annotated as negative in the source (Nassif 2021). Neither RCT supplies an absolute effect size, hazard ratio, or confidence interval in the curated excerpts, so the reader is referred to the evidence synthesis (Per-Study Endpoint Evidence) for the complete study × p-value matrix rather than to prose-restyled estimates.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_25","claim":"Several within-corpus tensions warrant explicit acknowledgement. First, on the indirectness gap axis, the two direct trials (Nassif 2021; Spertus 2022) must be read separately from the four indirect or review-level sources (Khanna 2026; Loutati 2026; Ryan 2018; Chen 2021); the curated excerpts do not support pooling direct and indirect evidence into a single effect estimate, and the evidence synthesis preserves that separation. Second, on the null vs positive axis, Loutati 2026 (positive on contextual other, observational) is in partial conflict with Chen 2021 (null on contextual other, preclinical), and the conflict is partially explained by endpoint layer (clinical event rates versus plaque histologic indices) and partially by study design (cohort versus murine experiment); readers should not interpret Chen 2021 as a refutation of Loutati 2026 without acknowledging that the two sources measure different things. Third, the directionality disagreement between Nassif 2021 (negative) and Spertus 2022 (unclear) within the same direct-RCT stratum cannot be resolved from the curated excerpts alone and is a genuine boundary condition of the present synthesis. Finally, Ryan 2018 — the only source explicitly positioned as a real-world comparative-effectiveness meta-analysis of four observational databases — supplies qualitative framing without extractable p-values in the curated excerpts, so its contribution to the contextual other class is contextual rather than quantitative; future updates should re-extract Ryan 2018 numerics before drawing comparative-effectiveness inferences. Across the corpus, the contextual other outcome class is the most numerate stratum of the SGLT2 inhibitor corpus but also the most internally heterogeneous, and any downstream anti-aging claim that rests on it must specify which sub-stratum (symptoms, structure, plaque biology, real-world events) is being invoked.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_26","claim":"Safety remains a separate Results slice for SGLT2 inhibitor (n=1; claims=11; positive signal in 1/1 sources; 1 review; single-source slice; hypothesis-generating) and is not pooled into adjacent endpoint classes. Nassif 2021 (NCT03030235) is a direct multicenter RCT in HFpEF reporting a constellation of p-values (P = 0.001, P = 0.003, P = 0.026, P = 0.007, P = 0.009, P = 0.03, P = 0.046, P = 0.06, P = 0.01) but with the source-coded direction flagged as 'negative,' meaning the primary functional endpoint did not deliver the anticipated benefit despite favorable signals in secondary biomarker readouts. By contrast, Metabolism to Microcirculation the Multifaceted 2026 catalogs vasoprotective mechanisms — dapagliflozin improving endothelial mitochondrial respiration in cell culture and murine models — that would predict hemodynamic and microcirculatory gains in vivo. The disagreement is not a contradiction but an evidence-type mismatch: preclinical and biomarker evidence is permitted to look unambiguously positive while the matched human functional RCT reads null or unfavorable. The boundary condition is the level of the outcome being measured — molecular microcirculatory flux, which the mechanistic review captures, is not equivalent to patient-reported or clinician-assessed functional status captured in HFpEF trials, a surrogate-vs-hard-outcome caution that aligns with Ioannidis 2005. What would resolve the tension is a human RCT powered on hard composite endpoints (mortality, hospitalization) rather than on biomarker surrogates or KCCQ-style symptom scores, ideally with prespecified microcirculatory substudies to confirm mechanistic engagement alongside clinical benefit.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_27","claim":"The longevity translation is the most fragile inference in the corpus. E 2026 — classified under the longevity outcome class — reports the HF-hospitalization pooled HR 0.65 (95% CI 0.59-0.72) finding but is anchored on indirect observational evidence and codes direction as 'unclear' on longevity per se. The mechanistic scaffolding (Metabolism to Microcirculation the Multifaceted 2026 on endothelial mitochondrial respiration; Chen 2021 on plaque instability in murine models) supports plausibility but is model-organism and biomarker evidence, not human mortality or healthspan evidence. This invokes the general caution registered by Ioannidis 2005 — surrogate endpoint shifts do not guarantee hard-outcome validity. The boundary condition is straightforward: SGLT2 inhibitors have credible mechanistic grounds to influence longevity-relevant biology (vascular aging, cardiorenal hemodynamics, metabolic substrate handling) but the sources in this corpus do not contain a human RCT with mortality or lifespan as a primary endpoint. The 'approximately one-third' reduction in HF hospitalization is encouraging but is not equivalent to a one-third reduction in mortality, and even E 2026's HR should not be re-stated as a longevity claim. Resolution would require either (a) a long-horizon RCT with mortality as the primary endpoint, or (b) high-quality individual-participant-data meta-analyses of completed trials with extended mortality follow-up. Until then, the appropriate hedge — and the one this synthesis adopts — is that the SGLT2-inhibitor anti-aging case is mechanistically coherent and clinically promising in selected hard outcomes, but its longevity translation in humans remains unestablished by the sources in hand.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_28","claim":"source E 2026 evaluated adults receiving SGLT2 inhibitors in an observational cohort design and reported outcomes against the longevity outcome class, with the source excerpts indicating a consistent reduction in heart failure hospitalisation rates across real-world use (pooled HR 0.65, 95% CI 0.59-0.72). The trial was framed as a meta-analysis of real-world effectiveness, drawing on data outside the randomised controlled setting, which positions the finding as indirect rather than as a primary longevity endpoint. Effect direction in the source is recorded as unclear, reflecting the ambiguity of mapping heart-failure hospitalisation endpoints onto longevity outcomes proper. Sample size, follow-up duration, and the exact absolute risk reduction figures are not specified in the available excerpt, so the discussion is limited to the proportional hazard reported.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_29","claim":"The p-value field in the source is recorded as P > 0.05, which is inconsistent with the magnitude of the reported hazard reduction and signals internal ambiguity in how statistical significance was determined within the observational corpus. Because the source does not supply a sample size, follow-up window, or dose stratification, no further quantitative claims can be derived without crossing into training-data numerics. the evidence synthesis carries the per-study endpoint decomposition referenced throughout this subsection.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]},{"claim_id":"claim_30","claim":"Mechanistically, the longevity signal in E 2026 rests on the same cardiovascular substrate that has been documented for SGLT2 inhibitors in mechanistic human studies and in clinical RCTs of heart failure outcomes: reduced preload, natriuresis, and improved ventricular loading conditions translate into fewer hospitalisation events, which in turn may bear on cumulative morbidity burden. The source is, however, framed as an observational cohort and is therefore best read as supporting contextual evidence rather than as a primary mechanistic demonstration. Because the outcome class is longevity rather than cardiovascular hospitalisation per se, the pathway connecting reduced HF admissions to longevity extension remains inferential. The mechanistic substrate underlying this functional finding is plausibly cardioprotective, but the source itself does not adjudicate the magnitude of any survival extension.","candidate_sources":[{"source_id":"source_1","study":"The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial","doi":"10.1038/s41591-021-01536-x","url":"https://doi.org/10.1038/s41591-021-01536-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_2","study":"Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease","doi":"10.1186/s13098-022-00929-3","url":"https://doi.org/10.1186/s13098-022-00929-3","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_3","study":"The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial","doi":"10.1038/s41591-022-01703-8","url":"https://doi.org/10.1038/s41591-022-01703-8","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"},{"source_id":"source_4","study":"Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis","doi":"10.1186/s12933-022-01476-x","url":"https://doi.org/10.1186/s12933-022-01476-x","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review-level"},{"source_id":"source_5","study":"Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes","doi":"10.1093/ehjcvp/pvag018","url":"https://doi.org/10.1093/ehjcvp/pvag018","support_kind":"candidate_source_row","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"primary"}]}]}