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Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure
Open accessAbstract
BACKGROUNDSodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes.More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODSIn this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy.The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTSDuring a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001).The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes.The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001).The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28ml per minute per 1.73 m 2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes.Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONSAmong patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes.(Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.govnumber, NCT03057977.
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In the citing paper
“Subgroup analyses from DAPA-CKD (117) and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/1.73m 2 .”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [119]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Direct evidence is provided by the DAPA-CKD, SCORED, EMPEROR-Reduced, and EMPEROR-Preserved trials, which enrolled such participants by design.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, notably, SGLT2i have been studied among patients without T2D who have CKD in the DAPA-CKD trial (and the soonto-be-published EMPA-KIDNEY trial) or who have heart failure (in the DAPA-HF, EMPEROR-Reduced, and EMPEROR-Preserved trials) and did not confer any increased risk of severe hypoglycemia or diabetic ketoacidosis among individuals without T2D.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“enrollment criteria included eGFR >60 mL/min/1.73m 2 , but efficacy was seen at eGFR >20 mL/min/1.73m 2 in people with heart failure.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [135]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250,(255)(256)(257)(298)(299)(300)(301)(302)(303)(304)(305)(306).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [303]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure (EMPEROR) trials (which provided clear evidence of efficacy and safety for empagliflozin among patients with eGFR ≥20 mL/min/1.73 m2 and HF) (54,57,58).”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [58]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clinical trials, such as EMPEROR-REDUCED (empagliflozin) and DAPA-CKD (dapagliflozin), have shown that SGLT-2 inhibitors have benefits in patients with heart failure and chronic kidney disease, regardless of the presence of diabetes.38,39”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [39]
The cited source says what the claim attributes to it.
In the citing paper
“The primary outcome among those with an eGFR $ 60 ml/min per 1.73 m 2 was HR: 0.67; 95% CI: 0.55 -0.83 and for those with eGFR < 60 ml/min per 1.73 m 2 was HR: 0.83; 95% CI: 0.69 -1.00.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“As seen in DAPA-HF, the primary outcome was similarly reduced for individuals with and without diabetes.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“the primary outcome of cardiovascular death or heart failure hospitalization occurred in 19.4% of the empagli fl ozin group and 24.7% of the placebo group (HR: 0.75; 95% CI: 0.65 -0.86).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“A composite kidney outcome HR of 0.50 (95% CI: 0.32 -0.77) was also reported.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
The cited source says what the claim attributes to it.
In the citing paper
“Similar results were obtained in clinical trials with empagliflozin (303).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [303]
The cited source says what the claim attributes to it.
In the citing paper
“Similar results were obtained in clinical trials with empagliflozin (291).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [291]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPEROR-Reduced 101 and EMPEROR-Preserved 102 trials, although not an exclusive CKD population, did allow enrollment of patients with an eGFR as low as 20 ml/min per 1.73 m 2.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPA-REG trial enrolled over 7000 patients with T2D, baseline glycated hemoglobin (HbA1c) of 7% -10%, established CVD (almost 100%), and an eGFR of at least 30 ml/min per 1.73 m 2 . 101”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The EMPEROR-Reduced and EMPEROR-Preserved trials, although not exclusive CKD populations, did allow enrollment participants with an eGFR as low as 20 ml/min per 1.73 m 2 .”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [101]
Experimental — accuracy not yet measuredIn the citing paper
“The EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial demonstrated a benefit of SGLT2 inhibition with empagliflozin to reduce both the risk and rate of heart failure hospitalizations.7”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [7]
In the citing paper
“Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those that focused on type 2 diabetes, heart failure with a reduced ejection fraction, and chronic kidney disease.1–8”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [7]
In the citing paper
“As previously reported,7 the 2 groups comprised patients with mild, moderate, and severe heart failure, as reflected by left ventricular ejection fraction and circulating levels of NT-proBNP, and were well-balanced with respect to baseline characteristics.”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [7]
In the citing paper
“In the EMPEROR-Reduced trial, empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure, a benefit that was driven primarily by an effect of the drug to reduce first and recurrent admissions for worsening heart failure.7”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [7]
In the citing paper
“In our original publication and in a meta-analysis of the DAPA-HF and EMPEROR-Reduced trials, we noted a somewhat lesser benefit in patients with ejection fraction of 31% to 40% and in patients with class III symptoms.”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [7]
In the citing paper
“Rates of worsening heart failure or cardiovascular death are lower among patients with heart failure who are treated with dapagliflozin and empagliflozin regardless of diabetes diagnosis.7,8”
From Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US (2021) · cites this paper as [8]
In the citing paper
“As for the morbidity, renal outcome and HHF, it was clear that SGLT-2i had more significant impact than finerenone, which might be explained by the special potency of SGLT-2i such as reducing blood glucose, reducing oxidative stress, losing weight, reducing uric acid, controlling blood pressure and improving renal ultrafiltration and hypoxia [65, 71–79].”
In the citing paper
“Multiple SGLT2i trials included subsets of participants without diabetes, who appear to have derived similar benefits as those with T2D, 8,14,18”
In the citing paper
“Treatment with empagliflozin improved quality of life.496”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [496]
In the citing paper
“The risk of a prespeci fi ed renal composite outcome (chronic dialysis, renal transplantation, or a sustained reduction in eGFR) was lower in the empagli fl ozin group than in the placebo group (1.6% in the empaglifl ozin group vs. 3.1% in the placebo group; HR 0.50 [95% CI 0.32 -0.77]).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Over a median follow-up of 16 months, those in the empagli fl ozin-treated group had a reduced risk of the primary outcome (HR 0.75 [95% CI 0.65 -0.86]; P < 0.001) and fewer total hospitalizations for heart failure (HR 0.70 [95% CI 0.58 -0.85]; P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Over a median follow-up of 16 months, those in the empagli fl ozin-treated group had a reduced risk of the primary outcome (HR 0.75 [95% CI 0.65 -0.86]; P < 0.001) and fewer total hospitalizations for heart failure (HR 0.70 [95% CI 0.58 -0.85]; P < 0.001).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“The effect of empagli fl ozin on the primary outcome was consistent irrespective of diabetes diagnosis at baseline.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [200]
In the citing paper
“Moreover, in the recent EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), SGLT2 inhibition did reduce renal events significantly, although that trial used a different renal composite outcome and had more renal events than in DAPA-HF (88 versus 67).”
From Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF (2021) · cites this paper as [21]
In the citing paper
“More recently, in a large trial using empagliflozin in patients with HFrEF, the rate of decline in eGFR was 2.28 (SD 0.23) mL·min–1·1.73 m–2 per year, which was reduced to 0.55 (0.23) in the SGLT2 inhibitor group.21”
From Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF (2021) · cites this paper as [21]
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Citations
Cites
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Items 901–1,000 of 1,012
Empagliflozin: A Review in Symptomatic Chronic Heart Failure
Frampton, J. E. (2022) · Drugs · doi:10.1007/s40265-022-01778-0 · Cited by 31
“The effect of empagliflozin on cardiorenal outcomes and health-related quality of life (HRQOL) has been evaluated in two large, randomized, double-blind, placebo-controlled, multinational, phase III trials in ambulant patients with HFrEF (EMPEROR-Reduced [22, 23]; Sect.”
BackgroundMethodInfluentialMoghaddam, N., Hawkins, N. M., McKelvie, R. S., Poon, S., Joncas, S. X., MacFadyen, J. R., Honos, G. N., Wang, J., Rojas‐Fernandez, C. H., Kok, M., et al. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2022.10.013 · Cited by 30
Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review
Ntentakis, D. P., Correa, V., Ntentaki, A. M., Delavogia, E., Narimatsu, T., Efstathiou, N. E., & Vavvas, D. G. (2023) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-023-06236-5 · Cited by 38
SGLT2 inhibitors in cardiovascular medicine
Varzideh, F., Kansakar, U., & Santulli, G. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvab039 · Cited by 32
“Another trial demonstrated that among patients receiving recommended therapy for HF, those treated with empagliflozin had a lower risk of cardiovascular death or HF hospitalization than those in the placebo group, independent from the presence of diabetes.(2) In addition, the effects of sotagliflozin, which also acts…”
BackgroundRenal Tubular Handling of Glucose and Fructose in Health and Disease
Vallon, V., & Nakagawa, T. (2021) · Comprehensive physiology · doi:10.1002/cphy.c210030 · Cited by 49
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Self-citationEmpagliflozin attenuates doxorubicin-induced cardiotoxicity by inhibiting the JNK signaling pathway
Chang, H., Hsu, H.-C., Fang, Y., Liu, P., & Liu, Y.-W. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116759 · Cited by 28
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“…SGLT2is, dapagliflozin and empagliflozin, reduce composite cardiovascular end-points in patients with both heart failure with reduced ejection fraction (HFrEF) [12,13] and heart failure with preserved ejection fraction (HFpEF) [11,50], which is a unique feature for heart failure therapies. therapies.”
Rosano, G. M. C., Quek, D. K., & Martínez, F. A. (2020) · Cardiac failure review · doi:10.15420/cfr.2020.23 · Cited by 28
“12]) compared to placebo.(9) There was also a significant reduction in the rate of renal disease progression, as measured by eGFR slope over time, in the empagliflozin group compared to patients receiving placebo (–0.”
BackgroundMethodResultInfluentialChambergo‐Michilot, D., Tauma‐Arrué, A., & Loli-Guevara, S. (2020) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2020.100690 · Cited by 30
“It was a placebo-controlled RCT that randomly assigned NYHA II-IV HFrEF patients to empagliflozin or placebo, concluding that the intervention significantly reduced cardiovascular death or HF hospitalization in absence of diabetes [29].”
MethodYerra, V. G., Batchu, S. N., Kabir, G., Advani, S. L., Liu, Y., Siddiqi, F. S., Connelly, K. A., & Advani, A. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07190-2 · Cited by 28
“For instance, in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced), the effect of empagliflozin in reducing the primary outcome of cardiovascular death or hospitalization for worsening heart failure was consistent in participants with or without di…”
ResultLi, X., Zhang, M.-W., Zhang, Z.-Z., Cao, Y., Liu, X.-Y., Miao, R., Xu, Y., Song, X.-F., Song, J.-W., Liu, Y., et al. (2021) · International Journal of Cardiology · doi:10.1016/j.ijcard.2021.05.029 · Cited by 28
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Azzam, O., Carnagarin, R., Lugo‐Gavidia, L. M., Nolde, J. M., Matthews, V. B., & Schlaich, M. P. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1959915 · Cited by 30
“was consistent regardless of presence or absence of T2D [58].”
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Heart failure and its treatment from the perspective of sympathetic nerve activity
Minatoguchi, S. (2021) · Journal of Cardiology · doi:10.1016/j.jjcc.2021.11.016 · Cited by 27
Kubota, Y., & Shimizu, W. (2022) · JACC Asia · doi:10.1016/j.jacasi.2022.03.009 · Cited by 29
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Self-citationAkiyama, H., Nishimura, A., Morita, N., & Yajima, T. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1111984 · Cited by 30
“Although EMPEROR-Reduced did not show a significant risk reduction for death from CV causes (HR 0.92, 95% CI 0.75 to 1.12) or death from any cause (HR 0.92, 95% CI 0.77 to 1.10), a meta-analysis of DAPA-HF and EMPEROR-Reduced showed significant risk reductions for both outcomes (67).”
BackgroundMethodInfluentialHeart Failure Pharmacological Management: Gaps and Current Perspectives
Severino, P., D’Amato, A., Prosperi, S., Myftari, V., Canuti, E. S., Francia, A. L., Cestiè, C., Maestrini, V., Lavalle, C., Badagliacca, R., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12031020 · Cited by 28
“4% in the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial [50] and 10.”
BackgroundAziri, B., Begić, E., Јаnkovic, S., Mladenović, Z., Stanetić, B., Kovačević-Preradović, T., Iglica, A., & Mujaković, A. (2023) · ESC Heart Failure · doi:10.1002/ehf2.14355 · Cited by 30
“With respect to safety considerations, it should be noted that the EMPEROR-Reduced trial in fact, listed the eGFR slope as one of the hierarchical endpoints; there was an initial drop in eGFR and a later stabilization, with a beneficial effect overall.(30) The same was seen in DAPA-HF, even in patients without diabete…”
BackgroundResultNephroprotective Properties of Antidiabetic Drugs
Gerdes, C., Muller, N., Wolf, G., & Busch, M. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12103377 · Cited by 30
“Unfortunately, no subgroup analyses of individuals with and without DM are available [71].”
BackgroundNeijenhuis, R. M. L., Nederend, M., Jongbloed, M. R. M., Kiès, P., Rotmans, J. I., Vliegen, H. W., Jukema, J. W., & Egorova, A. D. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1093201 · Cited by 28
Cardiovascular Diseases: Therapeutic Potential of SGLT-2 Inhibitors
Frąk, W., Hajdys, J., Radzioch, E., Szlagor, M., Młynarska, E., Rysz, J., & Franczyk, B. (2023) · Biomedicines · doi:10.3390/biomedicines11072085 · Cited by 35
“In the randomized EMPEROR-Reduced trial, 3730 patients with chronic HF (NYHA 2–4) and a left ventricular ejection fraction (LVEF) of 40% or less were screened to assess the effect of empagliflozin on the incidence of cardiovascular death or first HF hospitalization (the first outcome), as well as the rate of all HF ho…”
BackgroundRaiten, J. M., Morlok, A. P., D'Ambrosia, S., Ruggero, M. A., & Flood, J. (2023) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2023.10.011 · Cited by 32
The Ketogenic Effect of SGLT-2 Inhibitors—Beneficial or Harmful?
Koutentakis, M., Kuciński, J., Świeczkowski, D., Surma, S., Filipiak, K. J., & Gąsecka, A. (2023) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd10110465 · Cited by 30
Verma, S., McGuire, D. K., & Kosiborod, M. (2020) · Circulation · doi:10.1161/circulationaha.120.051122 · Cited by 28
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Sung, H., Hung, C., Tung, Y., Lin, C., Tsai, T., & Huang, K. (2024) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3784 · Cited by 27
“19,20 Consequently, the use of SGLT ‐ 2is is increasing year by year.”
BackgroundNovel Perspectives in Chronic Kidney Disease-Specific Cardiovascular Disease
Xu, C., Tsihlis, G., Chau, K., Trinh, K., Rogers, N. M., & Julovi, S. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052658 · Cited by 30
Chioncel, O. D., Čelutkienė, J., Bělohlávek, J., Kamzola, G., Lainščak, M., Merkely, B. P., Miličić, D., Nessler, J., Ristić, A. D., Sawiełajc, L., et al. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14687 · Cited by 28
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Self-citationPharmacologic Glycemic Management of Type 2 Diabetes in Adults---2024 Update
Shah, B. R., BAJAJ, H. S., Butalia, S., Dasgupta, K., Eurich, D. T., Jain, R., Leung, K., Mansell, K. D., & Simpson, S. H. (2024) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2024.08.002 · Cited by 32
Early combination therapy with SGLT2i and GLP ‐1 RA or dual GIP / GLP ‐1 RA in type 2 diabetes
Vale, C., Lourenço, I. M., Jordan, G., Golovaty, I., Torres, H., Moin, T., Buysschaert, M., Neves, J. S., & Bergman, M. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16077 · Cited by 29
Anti-senescence therapies: a new concept to address cardiovascular disease
Stojanović, S. D., Thum, T., & Bauersachs, J. K. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf030 · Cited by 32
Ferreira, J. P., Anker, S. D., Butler, J., Filippatos, G., Januzzi, J. L., Schueler, E., Panova‐Noeva, M., Wetzel, K., Prochaska, J. H., Pocock, S., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.03.503 · Cited by 31
Self-citationBozkurt, B., Rossignol, P., & Vassalotti, J. A. (2025) · European Journal of Heart Failure · doi:10.1002/ejhf.3683 · Cited by 32
SGLT2 Inhibitors: From Molecular Mechanisms to Clinical Outcomes in Cardiology and Diabetology
Stielow, M., Fijałkowski, Ł., Alaburda, A., Grześk, G., Grześk, E., Nowaczyk, J., & Nowaczyk, A. (2025) · Molecules · doi:10.3390/molecules30153112 · Cited by 30
“More recently, trials including DAPA-HF [9], EMPEROR-Reduced [10], EMPEROR-Preserved [11], SOLOIST-WHF [12], and DELIVER [13] have shown that these agents also improve outcomes in heart failure patients, independent of diabetic status.”
Fralick, M., Colacci, M., Thiruchelvam, D., Gomes, T., & Redelmeier, D. A. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14300 · Cited by 27
“Similar findings were observed in the recently published EMPEROR-Reduced Trial which compared empagliflozin to placebo in a similar patient population to those included in DAPA-HF.(9) However, whether similar benefits extend to a broader population of patients at lower baseline risk of heart failure or older adults is…”
InfluentialLam, D. W.-H., & Shaikh, A. (2021) · Kidney360 · doi:10.34067/kid.0000412021 · Cited by 29
Oka, S., Kai, T., Hoshino, K., Watanabe, K., Nakamura, J., Abe, M., & Watanabe, A. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-02024-3 · Cited by 27
“Furthermore, it was recently shown that SGLT2i treatment was associated with lowering the risk of cardiovascular death and hospitalization for HFrEF consistently from the early to late periods after the start of administration, regardless of the presence or absence of T2DM [9, 10].”
BackgroundPhenomapping Heart Failure with Preserved Ejection Fraction Using Machine Learning Cluster Analysis
Galli, E., Bourg, C., Kosmala, W., Oger, E., & Donal, E. (2021) · Heart Failure Clinics · doi:10.1016/j.hfc.2021.02.010 · Cited by 31
Heart failure population health considerations
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Transforming the Care of Patients with Diabetic Kidney Disease
Brosius, F. C., Cherney, D. Z. I., Gee, P. O., Harris, R. C., Kliger, A. S., Tuttle, K. R., & Quaggin, S. E. (2021) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.18641120 · Cited by 28
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Kolwelter, J., Bosch, A., Jung, S., Stabel, L., Kannenkeril, D., Ott, C., Bramlage, P., Schiffer, M., Achenbach, S. S., & Schmieder, R. E. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13622 · Cited by 27
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“In addition to its excellent glucose-lowering effect, recent studies demonstrated that empagliflozin markedly improved myocardial function in diabetic and non-diabetic heart failure (Fitchett et al., 2016; Santos-Gallego et al., 2019; Yurista et al., 2019; Packer et al., 2020).”
BackgroundKim, H. M., Hwang, I., Choi, W., Yoon, Y. E., & Cho, G. (2021) · Scientific Reports · doi:10.1038/s41598-021-01759-5 · Cited by 27
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“life and alleviated heart failure symptoms in HFrEF patients who described symptoms in New York Heart Association (NYHA) class II-IV despite optimal medical therapy [6,7].”
BackgroundResultRecent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review
Kim, J. A., Wu, L., Rodriguez, M., Lentine, K. L., Virk, H. U. H., Hachem, K. E., Lerma, E. V., Kiernan, M. S., Rangaswami, J., & Krittanawong, C. (2022) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2022.101509 · Cited by 33
SGLT2 Inhibitors in Acute Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Amin, N. U., Sabir, F., Amin, T., Sarfraz, Z., Sarfraz, A., Robles‐Velasco, K., & Chérrez-Ojeda, I. (2022) · Healthcare · doi:10.3390/healthcare10122356 · Cited by 27
“More recently, the U.S. Food and Drug Administration (FDA) approved empagliflozin in February 2022, for patients with HF regardless of LVEF to reduce the risk of cardiovascular death and hospitalization [22].”
BackgroundPractical Patient Care Considerations With Use of Vericiguat After Worsening Heart Failure Events
Rao, V. N., Dı́ez, J., Gustafsson, F., Mentz, R. J., Senni, M., Jankowska, E. A., & Bauersachs, J. K. (2022) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2022.10.431 · Cited by 27
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Cross-Talk of NADPH Oxidases and Inflammation in Obesity
Morawietz, H., Brendel, H., Diaba‐Nuhoho, P., Catar, R. A., Perakakis, N., Wolfrum, C., & Bornstein, S. R. (2023) · Antioxidants · doi:10.3390/antiox12081589 · Cited by 29
ナトリウム・グルコース共輸送体2（SGLT2）阻害薬カナグリフロジンは非糖尿病マウスの遅筋および速筋に異なる影響を及ぼす
Otsuka, H. (2023) · Kyushu University Institutional Repository (QIR) (Kyushu University) · Cited by 27
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Cardiac Substrate Utilization and Relationship to Invasive Exercise Hemodynamic Parameters in HFpEF
O’Sullivan, J., Li, M., Koay, Y. C., Wang, X., Guglielmi, G., Marques, F. Z., Nanayakkara, S., Mariani, J. A., Slaughter, E., & Kaye, D. M. (2024) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2023.11.006 · Cited by 26
SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation
Schmidt, K., Schmidt, A., Groß, S., Just, A., Pfanne, A., Fuchs, M., Jordan, M., Mohr, E., Pich, A., Fiedler, J., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-65410-9 · Cited by 29
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Sodium-Glucose Cotransporter-2 Inhibitors and Arrhythmias
Jaiswal, V., Ang, S. P., Kumar, D., Deb, N., Jaiswal, A., Joshi, A., NASIR, Y. M., Bandyopadhyay, D., Michos, E. D., Benjamin, E. J., et al. (2025) · JACC Advances · doi:10.1016/j.jacadv.2025.101615 · Cited by 26
Crispino, S. P., Segreti, A., Nafisio, V., Valente, D., Crisci, F., Ferro, A., Cavallari, I., Nusca, A., Ussia, G. P., & Grigioni, F. (2025) · Biomedicines · doi:10.3390/biomedicines13030608 · Cited by 32
“The first two randomized trials to investigate the effect of an SGLT2i compared with placebo in patients with HFrEF with and without T2D were the DAPA-HF [31] and the EMPEROR-Reduced [30].”
InfluentialTseng, P., Zeng, B., Hsu, C.-W., Hung, C., Carvalho, A. F., Stubbs, B., Chen, Y., Chen, T., Lei, W., Chen, J.-J., et al. (2025) · BMC Medicine · doi:10.1186/s12916-025-04018-w · Cited by 35
Greco, A., Canale, M. L., Quagliariello, V., Oliva, S., Tedeschi, A., Inno, A., Biasio, M. D., Bisceglia, I., Tarantini, L., Maurea, N., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104780 · Cited by 28
“…and Prevention of Adverse outcomes in Heart Failure) trial enrolled 4744 patients (58% non-diabetic) [41], and the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction) trial enrolled 3730 subjects (50.2% non-diabetic) [42].”
InfluentialButler, J., Zannad, F. M., Filippatos, G. S., Anker, S. D., & Packer, M. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa731 · Cited by 26
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“These findings ultimately led to the landmark EMPEROR-Reduced and DAPA-HF trials, which cemented these medications as part of the current armamentarium of guideline therapies.(3,5,28) Despite the overwhelming amount of data supporting their efficacy, GDMT (currently “quadruple therapy,” encompassing a beta blocker, RA…”
Razaghizad, A., Oulousian, E., Randhawa, V. K., Ferreira, J. P., Brophy, J. M., Greene, S. J., Guida, J., Felker, G. M., Fudim, M., Tsoukas, M. A., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024833 · Cited by 27
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“Despite the available evidence of the protective effect of this class of drugs on the decline of renal function and reduction in renal events, during 6 months follow-up, there was no statistically significant difference on the variation of the estimated GFR between groups, which may be explained by the more prolonged…”
ResultInfluentialSGLT2 Inhibitors and Heart Failure with Preserved Ejection Fraction
Jhund, P. S. (2022) · Heart Failure Clinics · doi:10.1016/j.hfc.2022.03.010 · Cited by 30
Scheen, A. J. (2022) · Diabetes & Metabolism · doi:10.1016/j.diabet.2022.101405 · Cited by 26
Afşar, B., & Afşar, R. E. (2022) · Pharmacological Reports · doi:10.1007/s43440-022-00442-4 · Cited by 28
“These drugs are also effective in patients with heart failure (HF) both with reduced ejection [2, 7] fraction and preserved ejection fraction [8].”
BackgroundMuneuchi, J., Sugitani, Y., Kobayashi, M., Ezaki, H., Yamada, H., & Watanabe, M. (2022) · Case Reports in Cardiology · doi:10.1155/2022/5243594 · Cited by 26
Management of Heart Failure With Reduced Ejection Fraction
Rashid, A. M., Khan, M. S., Fudim, M., DeWald, T. A., DeVore, A. D., & Butler, J. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.101596 · Cited by 31
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“In 2020, the EMPEROR-Reduced trial further showed that in patients with HFrEF, with or without type 2 diabetes, empagliflozin reduced cardiovascular mortality, heart failure hospitalization, and progression of heart failure[8].”
BackgroundMethodBöhm, M., Butler, J., Krawczyk, M. J., Mahfoud, F., Haring, B., Filippatos, G. S., Ferreira, J. P., Pocock, S., Brueckmann, M., Ofstad, A. P., et al. (2023) · European Journal of Heart Failure · doi:10.1002/ejhf.2922 · Cited by 27
Self-citationResidual Risk in Heart Failure and the Need for Simultaneous Implementation and Innovation
Fatima, K., Butler, J., & Fonarow, G. C. (2023) · European Journal of Heart Failure · doi:10.1002/ejhf.3005 · Cited by 27
Self-citationSeidu, S., Kunutsor, S. K., Topsever, P., & Khunti, K. (2022) · Endocrinology, Diabetes & Metabolism · doi:10.1002/edm2.303 · Cited by 25
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Self-citationCVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes
Schnell, O., Barnard-Kelly, K. D., Battelino, T., Ceriello, A., Larsson, H. E., Fernández‐Fernández, B., Forst, T. M., Frías, J. P., Gavin, J. R., Giorgino, F., et al. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02180-8 · Cited by 27
Telephone-Based Guideline-Directed Medical Therapy Optimization in Navajo Nation
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Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure
Hahn, V. S., Selvaraj, S., Sharma, K., & Shah, S. H. (2024) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2024.04.008 · Cited by 26
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“32,35,38–40].”
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Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria
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Self-citation
Metadata
- Authors
- Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., Jamal, W., Kimura, K., Schnee, J., Zeller, C., Cotton, D., Bocchi, E., Böhm, M., Choi, D.-J., Chopra, V., Chuquiure, E., Giannetti, N., Janssens, S., Zhang, J., Gonzalez Juanatey, J. R., Kaul, S., Brunner-La Rocca, H.-P., Merkely, B., Nicholls, S. J., Perrone, S., Pina, I., Ponikowski, P., Sattar, N., Senni, M., Seronde, M.-F., Spinar, J., Squire, I., Taddei, S., Wanner, C., & Zannad, F.
- Affiliations
- University of Leicester (GB)
- Harvard University (US)
- St. Michael's Hospital (CA)
- Kyushu University (JP)
- Boehringer Ingelheim (Germany) (DE)
- Seoul National University (KR)
- From Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas (M.P.); Imperial College (M.P.) and the Department of Medical Statistics, London School of Hygiene and Tropical Medicine (S.J.P.), London, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow (N.S.), and the Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, Leicester (I.S.) — all in the United...
- Cedars-Sinai Medical Center (US)
- University of Pisa (IT)
- ORCID
- Packer, Milton
- Anker, Stefan D.
- Butler, Javed
- Filippatos, Gerasimos
- Pocock, Stuart J.
- Januzzi, James
- Verma, Subodh
- Tsutsui, Hiroyuki
- Brueckmann, Martina
- Jamal, Waheed
- Kimura, Karen
- Schnee, Janet
- Zeller, Cordula
- Cotton, Daniel
- Bocchi, Edimar
- Böhm, Michael
- Choi, Dong-Ju
- Chopra, Vijay
- Giannetti, Nadia
- Janssens, Stefan
- Zhang, Jian
- Kaul, Sanjay
- Nicholls, Stephen J.
- Perrone, Sergio
- Ponikowski, Piotr
- Sattar, Naveed
- Senni, Michele
- Seronde, Marie-France
- Squire, Iain
- Taddei, Stefano
- Wanner, Christoph
- Zannad, Faiez
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-10-08
- Volume
- 383
- Issue
- 15
- Pages
- 1413-1424
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3081830235
- Semantic Scholar
- 9f762448aff37cda38166e57ac40bc13f0005f51
- Cited by
- 5,206
- References
- 10
- Citations by year
- 2026: 638 · 2025: 757 · 2024: 820 · 2023: 965 · 2022: 936 · 2021: 910 · 2020: 163
- FWCI
- 459.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- HAL (submittedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Lirias (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Boehringer Ingelheim
- Eli Lilly
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- empagliflozin, SGLT2 inhibitors, heart failure with reduced ejection fraction, cardiovascular mortality, hospitalization for worsening heart failure, renal outcomes, estimated glomerular filtration rate decline, genital tract infection, diabetes status, EMPEROR-Reduced trial
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glomerular Filtration Rate, Glucosides, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Stroke Volume, Proportional Hazards Models, Disease Progression, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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