{"doi":"10.1001/jamanetworkopen.2023.30754","title":"Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure","abstract":"<jats:sec id=\"ab-zoi230883-1\"><jats:title>Importance</jats:title><jats:p>Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-2\"><jats:title>Objectives</jats:title><jats:p>To estimate the time to benefit from SGLT2 inhibitors among patients with HF.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-3\"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-4\"><jats:title>Intervention</jats:title><jats:p>Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-5\"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-6\"><jats:title>Results</jats:title><jats:p>Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (<jats:italic>P</jats:italic> &amp;amp;lt; .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-7\"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.</jats:p></jats:sec>","journal":"JAMA Network Open","year":2023,"id":634498,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1645643,"name":"Zhiqiang Nie","orcid":null,"position":1,"is_corresponding":false},{"id":971370,"name":"Rui Shi","orcid":"0000-0002-6255-2658","position":2,"is_corresponding":false},{"id":1645644,"name":"Dahai Yu","orcid":null,"position":3,"is_corresponding":false},{"id":348529,"name":"Qi Wang","orcid":"0000-0003-0858-9393","position":4,"is_corresponding":false},{"id":861708,"name":"Fang Shao","orcid":"0000-0002-2551-2956","position":5,"is_corresponding":false},{"id":1645647,"name":"Guohong Wu","orcid":null,"position":6,"is_corresponding":false},{"id":1645651,"name":"Zhenqiang Wu","orcid":null,"position":7,"is_corresponding":false},{"id":1442716,"name":"Tao Chen","orcid":"0000-0001-6325-5260","position":8,"is_corresponding":false},{"id":613035,"name":"Chao Li","orcid":"0000-0001-7580-0924","position":9,"is_corresponding":false},{"id":1645642,"name":"KangYu Chen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure","abstract":"<jats:sec id=\"ab-zoi230883-1\"><jats:title>Importance</jats:title><jats:p>Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-2\"><jats:title>Objectives</jats:title><jats:p>To estimate the time to benefit from SGLT2 inhibitors among patients with HF.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-3\"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-4\"><jats:title>Intervention</jats:title><jats:p>Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-5\"><jats:title>Main Outcomes and Measures</jats:title><jats:p>The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-6\"><jats:title>Results</jats:title><jats:p>Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (<jats:italic>P</jats:italic> &amp;amp;lt; .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction.</jats:p></jats:sec><jats:sec id=\"ab-zoi230883-7\"><jats:title>Conclusions and Relevance</jats:title><jats:p>In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37615988","pmcid":"PMC10450563","openalex_id":"https://openalex.org/W4386116783","authors":[],"funders":[],"total_grants":0,"fwci":5.0024,"citation_percentile":0.96699967,"influential_citations":1,"citation_trend":[{"year":2024,"count":8},{"year":2025,"count":18},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1001/jamanetworkopen.2023.30754","host_type":"journal"},{"url":"https://doi.org/10.1001/jamanetworkopen.2023.30754","host_type":"GOLD"},{"url":"https://doi.org/10.1001/jamanetworkopen.2023.30754","host_type":"publisher"},{"url":"https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2808738/chen_2023_oi_230883_1692220326.97644.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37615988","host_type":"repository"},{"url":"https://orcid.org/0000-0002-5489-6450>","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10450563","host_type":"repository"},{"url":"https://eprints.whiterose.ac.uk/id/eprint/202862/1/chen_2023_oi_230883_1692220326.97644.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10450563","host_type":"Europe_PMC"}],"fields_of_study":["Diabetes Treatment and Management","Heart Failure Treatment and Management","Hyperglycemia and glycemic control in critically ill and hospitalized patients","Medicine"],"mesh_terms":["Sodium-Glucose Transporter 2 Inhibitors","Aged","Diabetes Mellitus, Type 2","Female","Glucose","Heart Failure","Humans","Male","Sodium","Randomized Controlled Trials as Topic"],"keywords":["Medicine","Heart failure","Hazard ratio","Placebo","Internal medicine","Population","Statistical significance","Randomized controlled trial","Clinical trial","Confidence interval","Alternative medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:45:47.290587Z","pmid":null,"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":[]}