{"doi":"10.1002/ejhf.2172","title":"Sodium–glucose co‐transporter 2 inhibitors: strength of evidence for a cardio‐renal‐metabolic therapy","abstract":"This article refers to ‘Prevention of heart failure events with sodium–glucose co-transporter 2 inhibitors across a spectrum of cardio-renal-metabolic risk’ by K. Bhatia et al., published in this issue on pages 1002–1008. Sodium–glucose co-transporter 2 (SGLT2) inhibitors are potent antidiabetic agents for patients with type 2 diabetes mellitus (T2DM) that regulate glycaemic status through a non-insulin-dependent mechanism of stimulating glucose excretion in urine. SGLT2 inhibitor therapy is now a guideline-recommended approach for glycaemic control and cardiovascular risk reduction among high-risk T2DM patients. The SGLT2 inhibitors have had a serendipitous expedition into the arena of cardiovascular risk reduction and heart failure management in specific. The data from initial investigations of SGLT2 inhibitors demonstrated that apart from reducing hyperglycaemia, this medication class reduced arterial stiffness, vascular resistance, blood pressure, body weight, visceral adiposity, and albuminuria.1 These cardiovascular benefits prompted the evaluation of the impact of empagliflozin on cardiovascular outcomes among individuals with high-risk [having atherosclerotic cardiovascular diseases (ASCVD)] T2DM in the EMPA-REG OUTCOME trial.1 The results indicated a lower risk of adverse cardiovascular events and all-cause mortality among patients receiving empagliflozin compared with placebo. While glycaemic control is anticipated to contribute to cardiovascular risk reduction, antidiabetic agents more potent than SGLT2 inhibitors did not previously extend such a cardiovascular benefit. Spurred by the promising results, similar trials using dapagliflozin (DECLARE–TIMI 58), canagliflozin (CANVAS Program), and ertugliflozin (VERTIS CV) were completed in T2DM patients with ASCVD or having a high risk of developing ASCVD.2-4 These studies demonstrated a similar signal for reducing adverse cardiovascular outcomes.2-4 Interestingly, these initial SGLT2 inhibitor clinical trials observed a lower risk of adverse renal outcomes (defined by varying definitions of composite renal outcomes) among those randomized to the SGLT2 inhibitor medication arm.1-4 Encouraged by these compelling data, the CREDENCE study demonstrated that canagliflozin effectively reduced the risk of renal failure and cardiovascular events among people with diabetes and chronic kidney disease (CKD).5 Subsequently, the DAPA-CKD trial demonstrated that among CKD patients both with and without T2DM, dapagliflozin was efficacious in reducing the risk of renal failure, i.e. reduction in renal function, or cardiorenal cause of death.6 The recently completed SCORED trial among T2DM patients with CKD also demonstrated the efficacy of sotagliflozin, a combined SGLT1/2 inhibitor, for reducing adverse cardiovascular outcomes.7 Heart failure hospitalizations account for ∼$11 billion per annum in annual spending in the United States, with a concerning temporal trend for an increase in the heart failure hospitalization burden.8 The landmark DAPA-HF study demonstrated the efficacy of dapagliflozin in reducing heart failure hospitalizations and cardiovascular mortality among heart failure with reduced ejection fraction (HFrEF) patients.9 This was followed closely by the EMPEROR-Reduced study that demonstrated the efficacy of empagliflozin for reducing adverse cardiovascular outcomes in HFrEF.10 The recently concluded SOLOIST-WHF study that enrolled heart failure patients with T2DM across the spectrum of ejection fraction close to discharge following heart failure hospitalization demonstrated the cardiovascular benefits of sotagliflozin in worsening heart failure.11 In this issue of the Journal, Bhatia et al.12 summarize the effect of SGLT2 inhibitor therapy in preventing heart failure hospitalization and composite cardiovascular outcome (heart failure hospitalization or cardiovascular mortality) across diverse population groups. The article presents a high-quality data synthesis exercise ","journal":"European Journal of Heart Failure","year":2021,"id":210212,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51222,"name":"Pankaj Arora","orcid":"0000-0003-2420-3550","position":1,"is_corresponding":false},{"id":301658,"name":"Vibhu Parcha","orcid":"0000-0002-4993-8177","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-18T23:52:08.869117Z","pmid":"33779117","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":[]}