{"doi":"10.1002/ejhf.3240","title":"Time to Clinical Benefit with Sotagliflozin in Patients with Type 2 Diabetes and Chronic Kidney Disease: Insights from the SCORED Randomized Trial","abstract":"Sotagliflozin is a dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibitor that reduces heart failure (HF) outcomes in adults with type 2 diabetes and high cardiovascular (CV) risk.1, 2 Understanding the time-to-benefit with therapy can inform the urgency with which to prescribe. SCORED was a randomized, double-blind study of patients with type 2 diabetes (glycated haemoglobin ≥7%), chronic kidney disease (estimated glomerular filtration rate 25–60 ml/min/1.73 m2 of body surface area), and additional risk factors for CV disease.1 Patients were randomized 1:1 to sotagliflozin or placebo. The primary endpoint was a composite of CV death, hospitalization for HF, or urgent visit for HF. The secondary endpoint was total hospitalizations for HF and urgent visits for HF. In this post hoc analysis, the hazard ratio (HR) of sotagliflozin compared with placebo was assessed for each outcome continuously from time of randomization. The exact day after randomization when the treatment effect of therapy reached statistical significance (p < 0.05) and remained statistically significant for the duration of follow-up was determined. SCORED was approved by the relevant health authorities, institutional review boards, or ethics committees at each trial site. The final cohort consisted of 10 584 patients. Median age of this group was 69 years, with 44.9% female. Median follow-up was 16.0 months. Over the entire study period, sotagliflozin compared with placebo reduced the risk of the primary endpoint (HR 0.74; 95% confidence interval [CI] 0.63–0.88; p < 0.001), with 5.6 events per 100 person-years in the sotagliflozin group and 7.5 events per 100 person-years in the placebo group. A sustained significant reduction in the outcome was observed at 95 days after randomization (HR 0.70, 95% CI 0.50–0.98; Figure 1). Sotagliflozin compared with placebo similarly reduced the risk of the secondary endpoint (HR 0.67, 95% CI 0.55–0.82; p < 0.001), with 3.5 events per 100 person-years in the sotagliflozin group and 5.1 events per 100 person-years in the placebo group. A sustained significant reduction was observed at 115 days after randomization (HR 0.70, 95% CI 0.49–1.00; Figure 1). Among patients in SCORED, sotagliflozin improved HF outcomes, with statistically significant improvements observed as soon as 95 days from randomization. This reduction was sustained throughout the study period. The rapid time to clinical benefit with sotagliflozin in these clinically stable outpatients indicates the importance of immediate initiation of therapy. Beneficial effects were observed early, with the continuous analysis suggesting a steady state of treatment benefit in the first month, which may indicate rapid biological benefits (Figure 1). Clinical inertia in prescribing SGLT inhibitor therapy can result in missed opportunities for preventing HF events,3 and starting therapy quickly, potentially at index admission, could lead to meaningful improvement in HF outcomes.4 Currently, most eligible patients are not prescribed an SGLT inhibitor at hospital discharge, despite evidence demonstrating benefit and safety for initiating therapy during a hospital admission.5 Limitations of the present analysis include that detection of timing of significant benefit is affected by event rate and sample size. In conclusion, among patients in SCORED, sotagliflozin reduced HF outcomes with significant benefit seen early and sustained throughout the study period. This study was supported by Lexicon Pharmaceuticals. Conflict of interest: R.A. is involved in research funded by the Bristol Myers Squibb-Pfizer alliance, a consultant for Lexicon Pharmaceuticals, and involved in a clinical trial funded by Novartis. D.L.B. serves as the Chair of SCORED with research funding paid to Mount Sinai and discloses the following relationships – Advisory Board: Angiowave, Bayer, Boehringer Ingelheim,CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Lev","journal":"European Journal of Heart Failure","year":2024,"id":459432,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3774,"name":"Deepak L. Bhatt","orcid":"0000-0002-1278-6245","position":1,"is_corresponding":false},{"id":932871,"name":"Michael Szarek","orcid":"0000-0002-0046-0264","position":2,"is_corresponding":false},{"id":276836,"name":"Lawrence A. Leiter","orcid":"0000-0002-1040-6229","position":3,"is_corresponding":false},{"id":255773,"name":"Christopher P. Cannon","orcid":"0000-0003-4596-2791","position":4,"is_corresponding":false},{"id":55170,"name":"Renato D. Lópes","orcid":"0000-0003-2999-4961","position":5,"is_corresponding":false},{"id":578673,"name":"Michael J. Davies","orcid":"0000-0002-5196-6919","position":6,"is_corresponding":false},{"id":604604,"name":"Phillip Banks","orcid":"0009-0001-7333-8374","position":7,"is_corresponding":false},{"id":98761,"name":"Bertram Pitt","orcid":"0000-0001-5880-275X","position":8,"is_corresponding":false},{"id":79684,"name":"Philippe Gabríel Steg","orcid":"0000-0001-6896-2941","position":9,"is_corresponding":false},{"id":623887,"name":"Rahul Aggarwal","orcid":"0000-0002-4746-8511","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T02:03:55.280882Z","pmid":"38629597","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":[]}