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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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“5 , 2 0 2 2 Yeoh et al M A Y 2 0 2 2 : 3 0 6 – 3 1 8 Hyponatremia and Dapagliflozin Effect: DAPA-HF 307 AB BR E V I A T I O N S AND ACRONYM S eGFR = estimated glomerular filtration rate HF = heart failure HFrEF = heart failure and reduced ejection fraction KCCQ-TSS = Kansas City Cardiomyopathy Questionnaire-total symp…”
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Lyu, Y. S., Oh, S. K., Kim, J. H., Kim, S. Y., & Jeong, M. H. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01914-4 · Cited by 32
“The benefits of SGLT2i were first established in patients with HF with reduced ejection fraction [39, 40], and a recently published large-scale study revealed that these effects were also significant in patients with HF with preserved ejection fraction [41, 42].”
BackgroundDrug repurposing for cardiovascular diseases: New targets and indications for probenecid
Onódi, Z., Koch, S. E., Rubinstein, J., Ferdinandy, P., & Varga, Z. V. (2022) · British Journal of Pharmacology · doi:10.1111/bph.16001 · Cited by 31
“outcomes, proving that drug repurposing is a viable strategy for drug development in cardiovascular diseases (Packer et al., 2020; Ridker et al., 2017).”
BackgroundGregg, E. W., Patorno, E., Karter, A. J., Mehta, R., Huang, E. S., White, M. J., Patel, C. J., McElvaine, A. T., Cefalu, W. T., Selby, J. V., et al. (2023) · Diabetes Care · doi:10.2337/dc22-1438 · Cited by 34
Gourdy, P., Schiele, F., Halimi, J., Kownator, S., Hadjadj, S., & Valensi, P. E. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1227769 · Cited by 34
“This recommendation was mainly based on results from the EMPEROR-Reduced (EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure with Reduced Ejection Fraction) (49) and DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) (50) trials.”
BackgroundMethodFerreira, J. P., Butler, J., Anker, S. D., Januzzi, J. L., Panova‐Noeva, M., Reese‐Petersen, A. L., Sattar, N. A., Schueler, E., Pocock, S., Filippatos, G. S., et al. (2023) · European Journal of Heart Failure · doi:10.1002/ejhf.3101 · Cited by 32
“30,3 1 The primary endpoint for both trials was the combined risk of cardiovascular death or hospitalization for HF.”
BackgroundSelf-citationCurrent Approaches to Worsening Heart Failure: Pathophysiological and Molecular Insights
D’Amato, A., Prosperi, S., Severino, P., Myftari, V., Francia, A. L., Cestiè, C., Pierucci, N., Marek‐Iannucci, S., Mariani, M. V., Germanò, R., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031574 · Cited by 31
“Two of the main trials concerning the use of these drugs, the DAPA-HF [42] and EMPEROR-Reduced [43] trials, analyse the use of Dapagliflozin and Empagliflozin in terms of time to first occurrence of hospitalization for WHF rather than in terms of the therapy of WHF itself.”
MethodPolychronopoulou, E., Bourdon, F., & Teta, D. (2024) · Frontiers in Nephrology · doi:10.3389/fneph.2024.1332397 · Cited by 31
Natale, P., Tunnicliffe, D. J., Toyama, T., Palmer, S. C., Saglimbene, V. M., Ruospo, M., Gargano, L., Stallone, G., Gesualdo, L., & Strippoli, G. F. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015588.pub2 · Cited by 36
Pathophysiology and emerging biomarkers of cardiovascular-renal-hepato-metabolic syndrome
Nzobokela, J., Muchaili, L., Mwambungu, A., Masenga, S. K., & Kirabo, A. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1661563 · Cited by 36
“From a biomarker perspective, therapy with SGLT2 inhibitors results in decreased levels of urinary albumin-to-creatinine ratio (UACR), KIM-1, sTNFR1, and NT-proBNP, reflecting improvements in both renal and cardiac stress profiles (168).”
Myopathy Associated With Statins and SGLT2 – A Review of Literature
Gupta, R., Alcantara, R., Popli, T., Mahajan, S., Tariq, U., Dusaj, R., & Malik, A. H. (2020) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2020.100765 · Cited by 32
Empagliflozin Inhibits IL-1β-Mediated Inflammatory Response in Human Proximal Tubular Cells
Pirklbauer, M., Sallaberger, S., Staudinger, P., Corazza, U., Leierer, J., Mayer, G. J., & Schramek, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105089 · Cited by 31
“In this regard, large clinical trials recently demonstrated renal benefit of SGLT2i irrespective of the presence or absence of diabetes mellitus in CKD [6] and heart failure [7] patients.”
BackgroundRecent advances in pharmacological treatment of heart failure
Iacoviello, M., Palazzuoli, A., & Gronda, E. (2021) · European Journal of Clinical Investigation · doi:10.1111/eci.13624 · Cited by 35
Packer, M., Zannad, F. M., Butler, J., Filippatos, G. S., Ferreira, J. P., Pocock, S., Brueckmann, M., Zeller, C., Hauske, S. J., Anker, S. D., et al. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2334 · Cited by 31
Self-citationRole of CCR2-Positive Macrophages in Pathological Ventricular Remodelling
Yerra, V. G., & Advani, A. (2022) · Biomedicines · doi:10.3390/biomedicines10030661 · Cited by 37
“Similarly, an accumulation of macrophages has been reported in LV myocardial biopsies of patients with hypertension and HFpEF [35].”
BackgroundInfluentialCardiorenal Syndrome: An Updated Classification Based on Clinical Hallmarks
Pliquett, R. U. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11102896 · Cited by 31
“Therapy of heart failure with preserved ejection fraction has been updated as well: the sodium-glucose-transporter-2 inhibitor Empagliflozin has become a first-line therapy in patients with and without type-2-diabetes comorbidity [47].”
BackgroundLi, C., Yu, J., Hockham, C., Perkovic, V., Neuen, B. L., Badve, S. V., Houston, L., Lee, V. Y., Barraclough, J., Fletcher, R. A., et al. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14772 · Cited by 31
New strategies and therapies for the prevention of heart failure in high‐risk patients
Hammond, M. M., Everitt, I., & Khan, S. S. (2022) · Clinical Cardiology · doi:10.1002/clc.23839 · Cited by 37
SGLT2 Inhibitors and Safety in Older Patients
Pollack, R. M., & Cahn, A. (2022) · Heart Failure Clinics · doi:10.1016/j.hfc.2022.03.002 · Cited by 31
Abdin, A., Bauersachs, J. K., Soltani, S., Eden, M., Frey, N., & Böhm, M. (2022) · ESC Heart Failure · doi:10.1002/ehf2.14197 · Cited by 33
“Implementation of an SGLT-2i in HFrEF therapy is generally straightforward due to its favourable tolerability profile and its ease of administration (one dose, without titration).(8,27,28)”
BackgroundSelf-citationZhu, Z., Zeng, Q., Liu, Q., Wen, J., & Chen, G. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.44652 · Cited by 31
Evolving Diagnostic and Management Advances in Coronary Heart Disease
Ribeiro, M. D. O. L., Correia, V. M., de Oliveira, L. L. H., Soares, P. R., & Scudeler, T. L. (2023) · Life · doi:10.3390/life13040951 · Cited by 32
Canagliflozin mitigates carfilzomib-induced endothelial apoptosis via an AMPK-dependent pathway
Dabour, M. S., Abdelgawad, I. Y., Grant, M. K. O., El-Sawaf, E. S., & Zordoky, B. N. M. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114907 · Cited by 31
Repurposing drugs targeting metabolic diseases for cancer therapeutics
Pillai U, J., Ray, A., Maan, M., & Dutta, M. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103684 · Cited by 31
Pathophysiological basis of the cardiological benefits of SGLT-2 inhibitors: a narrative review
Panico, C., Bonora, B. M., Camera, A., Chilelli, N. C., Prato, G. D., Favacchio, G., Grancini, V., Resi, V., Rondinelli, M., Zarra, E., et al. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01855-y · Cited by 33
Jaiswal, A., Jaiswal, V., Ang, S. P., Hanif, M., Vadhera, A., Agrawal, V., Kumar, T., Nair, A. M., Borra, V., Garimella, V., et al. (2023) · Medicine · doi:10.1097/md.0000000000034693 · Cited by 41
“EMPEROR-Reduced and DAPA-HF trials showed a similar rate of AKI in both SGLT2 inhibitors and placebo groups in HF with impaired renal function patients.[14,15] A meta-analysis conducted by Neuen et al[40] showed a significantly reduced risk of AKI, end-stage renal disease, and the risk of dialysis, transplantations, o…”
Antifibrotic effects of sodium-glucose cotransporter-2 inhibitors: A comprehensive review
Shakour, N., Karami, S., Iranshahi, M., Butler, A. E., & Sahebkar, A. (2023) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2023.102934 · Cited by 32
Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Light, P. E. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab563 · Cited by 28
SGLT2 inhibitors: an evidence-based update on cardiovascular implications
Forzano, I., Wilson, S. M., Lombardi, A., Jankauskas, S. S., Kansakar, U., Mone, P., Varzideh, F., & Santulli, G. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2263354 · Cited by 33
“[94] EF: Ejection Fraction; I/R: Ischemia/Reperfusion; HF: Heart Failure; HFD + STZ: high-fat diet/streptozotocin; KO: Knock-Out; LV: Left Ventricular; SGLT2: Sodium – glucose cotransporter 2; T2DM: Type 2 Diabetes Mellitus. in HF ) [19], the EMPEROR-Reduced ( Empagliflozin Outcome Trial in Patients With Chronic HF Wi…”
BackgroundNephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches
Frățilă, G., Lupusoru, G. E., Sorohan, B. M., Obrișcă, B., Mocanu, V., Lupușoru, M. O. D., & Ismail, G. (2024) · Biomedicines · doi:10.3390/biomedicines12030569 · Cited by 35
Gonzalez, J., & Dave, C. V. (2024) · BMC Cardiovascular Disorders · doi:10.1186/s12872-024-03961-5 · Cited by 35
“…[2], and dapagliflozin [3] reduced the incidence of hospitalization for heart failure (HHF), spurring dedicated trials in patients with heart failure with reduced ejection fraction (HFrEF) [4, 5], and subsequently, patients with heart failure with preserved ejection fraction (HFpEF) [6, 7].”
BackgroundWang, W., Gao, Y., Wang, J., Ji, C., Gu, H., Yuan, X., Yang, S., & Wang, X. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.124.036789 · Cited by 31
Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction
van Essen, B. J., Ceelen, D. C. H., Ouwerkerk, W., Teng, T. K., Tharshana, G. N., Hew, F. M., Butler, J., Zannad, F. M., Lam, C. S. P., Ezekowitz, J. A., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.08.054 · Cited by 35
Self-citationGalli, M., Abbate, A., Bonaca, M. P., Crea, F., Forte, M., Frati, G., Gaudino, M. F. L., Gibson, C. M., Gorog, D. A., Mehran, R., et al. (2026) · Nature Reviews Cardiology · doi:10.1038/s41569-026-01249-z · Cited by 41
Bhatia, K., Jain, V., Gupta, K., Bansal, A., Fox, A., Qamar, A., Damman, K., & Vaduganathan, M. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2135 · Cited by 30
Ameri, P., Bertero, E., Maack, C., Teerlink, J. R., Rosano, G. M. C., & Metra, M. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvab033 · Cited by 31
Savarese, G., Uijl, A., Lund, L. H., Anker, S. D., Asselbergs, F. W., FITCHETT, D. H., Inzucchi, S. E., Koudstaal, S., Ofstad, A. P., Schrage, B., et al. (2021) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2021.05.012 · Cited by 29
“Our results in predicted HFrEF are consistent, overall, with the EMPEROR-Reduced trial, where empagliflozin reduced the primary outcome, which was a composite of CV death or HF hospitalization, by 25% (by 28% in patients with diabetes), whereas we observed a 21% risk reduction in our EMPA-REG OUTCOME analysis.(7)”
BackgroundResultInfluentialSelf-citationVolpe, M., Gallo, G., Modena, M. G., Ferri, C., Desideri, G., Tocci, G., Members of the Board of the Italian Society of Cardiovascular Prevention, Bellone, S., Bertolotti, M., Biffi, A., et al. (2022) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-021-00503-4 · Cited by 30
Li, N., Zhou, G., Zheng, Y., Lv, D., Zhu, X., Wei, P., Zheng, M., Liu, S., Zhou, E., Sun, W., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0261986 · Cited by 30
Zhou, K., Zi, X., Song, J., Zhao, Q., Liu, J., Bao, H., & Li, L. (2022) · Molecules · doi:10.3390/molecules27196221 · Cited by 30
“The adverse reactions of SGLT2i include genital mycotic infections and diabetic ketoacidosis [9,10].”
BackgroundKarasik, A., Lanzinger, S., Tan, E. C.-H., Yabe, D., Kim, D. J., Sheu, W. H., Cohen, C. M., Holl, R. W., Ha, K. H., Khunti, K., et al. (2023) · Diabetes & Metabolism · doi:10.1016/j.diabet.2022.101418 · Cited by 30
Yuan, Y., Sun, M., Jin, Z., Chen, Z., Ye, H., & Weng, H. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175560 · Cited by 30
Nakashima, M., Nakamura, K., Nishihara, T., Ichikawa, K., Nakayama, R., Takaya, Y., Toh, N., Akagi, S., Miyoshi, T., Akagi, T., et al. (2023) · Nutrients · doi:10.3390/nu15030748 · Cited by 34
Fu, E. L., Patorno, E., Everett, B. M., Vaduganathan, M., Solomon, S. D., Levin, R., Schneeweiß, S., & Desai, R. J. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad273 · Cited by 30
SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation
Klen, J., & Dolžan, V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071995 · Cited by 30
“04) in composite kidney outcome: doubling of serum creatinine, kidney replacement therapy, or death from kidney causes [64]”
BackgroundRisk of perioperative discontinuation of SGLT2 inhibitors
Oosterom-Eijmael, M. J. P., Hermanides, J., van Raalte, D. H., & Hulst, A. H. (2024) · British Journal of Anaesthesia · doi:10.1016/j.bja.2024.05.004 · Cited by 32
Vernstrøm, L., Gullaksen, S., Sørensen, S. S., Funck, K. L., Laugesen, E., & Poulsen, P. L. (2024) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15464 · Cited by 30
“4,8,9 In contrast, the effect of GLP-1RAs on major CV events is evident later and driven by a reduction in the incidence of ischaemic events (stroke in particular), indicating anti-atherogenic effects.”
BackgroundPinto, L. C. F., Rados, D. R. V., Remonti, L. R., Viana, M. V., Leitão, C. B., & Gross, J. L. (2022) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000440 · Cited by 32
“Moreover, more recent studies, such as the Declare TIMI 58 trial, also did not present extractable results of glycemic control in randomized patients (10), and neither did the trials that randomized patients with heart failure to SGLT-2 inhibitors, DAPA-HF, Emperor Reduced and Emperor Preserved Trials (21-23).”
BackgroundResultExtrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis
McEwan, P. C., Boyce, R., Sánchez, J. J. G., Sjöström, C. D., Stefánsson, B. V., NOLAN, S. T., Correa‐Rotter, R., Rossing, P. R., Chertow, G. M., McMurray, J. J. V., et al. (2022) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfac280 · Cited by 29
“…treatment option for patients with T2DM, with trials having demonstrated considerable additional therapeutic value to patients with heart failure [12, 13] and diabetic kidney disease [14–16 CKD and albuminuria, showing the value of SGLT2 inhibitors in patients with and without T2DM [17].”
Yang, T., & Zhang, D. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101884 · Cited by 30
Yaseen, A., & Lahiri, S. W. (2023) · Clinical Diabetes · doi:10.2337/cd22-0100 · Cited by 37
Jhund, P. S., Claggett, B. L., Talebi, A., Butt, J. H., Gasparyan, S. B., Wei, L., McCaw, Z. R., Wilderäng, U., Bengtsson, O., Desai, A. S., et al. (2023) · JAMA Cardiology · doi:10.1001/jamacardio.2023.0711 · Cited by 34
Diallo, A., Carlos‐Bolumbu, M., & Galtier, F. (2023) · Acta Diabetologica · doi:10.1007/s00592-023-02154-4 · Cited by 35
“Therefore, a total of 19 reports from 18 CVO trials fulfilled the [18–36].”
BackgroundVaziri, Z., Saleki, K., Aram, C., Alijanizadeh, P., Pourahmad, R., Azadmehr, A., & Ziaei, N. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115686 · Cited by 31
Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF
Trum, M., Riechel, J., Schollmeier, E., Lebek, S., Hegner, P., Reuthner, K., Heers, S., Keller, K., Wester, M., Klatt, S., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae095 · Cited by 29
Kasperová, B. J., Mráz, M., Svoboda, P., Hlaváček, D., Kratochvílová, H., Módos, I., Vrzáčková, N., Ivák, P., Janovská, P., Kobets, T., et al. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02298-9 · Cited by 31
“[9–12].”
Parwani, A. S., Kääb, S., Friede, T., Tilz, R. R., Bauersachs, J. K., Frey, N., Hindricks, G., Lewalter, T., Rienstra, M., Rillig, A., et al. (2024) · European Journal of Heart Failure · doi:10.1002/ejhf.3373 · Cited by 30
Cardiotoxicity of Anthracyclines
Balough, E. M., Ariza, A., Asnani, A. H., & Hoeger, C. W. (2024) · Cardiology Clinics · doi:10.1016/j.ccl.2024.08.002 · Cited by 29
Pană, M.-A., Boulmpou, A., İleri, Ç., Manzi, G., Golino, M., Ostojic, M., Galimzhanov, A. M., Busnatu, Ș., Mega, S., & Perone, F. (2025) · Medicina · doi:10.3390/medicina61020211 · Cited by 34
“Ranolazine is another agent available for the treatment of angina, particularly for patients with refractory symptoms, as it improves myocardial efficiency without significantly affecting heart rate or blood pressure [93,95].”
Standardized Definitions of Changes in Kidney Function in Trials of Heart Failure
Lala, A., Coca, S. G., Feinman, J., HAMO, C. E., Fiuzat, M., Abraham, W. T., O’Connor, C. M., Lindenfeld, J., Januzzi, J. L., Cavagna, I., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.11.041 · Cited by 31
Self-citationSGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors
Wing, S., Ray, J. G., Yau, K., Jeyakumar, N., Abdullah, S., Luo, B., Cherney, D. Z. I., Harel, Z., Hundemer, G. L., Mavrakanas, T. A., et al. (2025) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2025.0686 · Cited by 29
Cardiovascular, Kidney, Liver, and Metabolic Interactions in Heart Failure: Breaking Down Silos
Lee, C. J. M., Kosyakovsky, L. B., Khan, M. S., Wu, F., Chen, G., Hill, J. A., Ho, J. E., Foo, R., & Zannad, F. M. (2025) · Circulation Research · doi:10.1161/circresaha.125.325602 · Cited by 33
Self-citationPavlović, N., Todorović, P., Maglica, M., Kumrić, M., Vukojević, K., Pogorelić, Z., & Božić, J. (2025) · Biomolecules · doi:10.3390/biom15111572 · Cited by 31
“The EMPEROR-Reduced trial confirmed that empagliflozin lowered this composite endpoint by 25% and slowed renal decline [117].”
Contemporary Management of Heart Failure in Patients With Diabetes
Shaw, J. A., & Cooper, M. E. (2020) · Diabetes Care · doi:10.2337/dc20-2173 · Cited by 29
Verma, S., Anker, S. D., Butler, J., & Bhatt, D. L. (2020) · ESC Heart Failure · doi:10.1002/ehf2.13148 · Cited by 30
Self-citationKorkmaz‐Icöz, S., Kocer, C., Sayour, A. A., Kraft, P., Benker, M. I., Abulizi, S., Georgevici, A., Brlecic, P., Radovits, T., Loganathan, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157774 · Cited by 29
“Furthermore, two recent clinical trials (EMPEROR-Reduced [10] and DAPA-HF [11]) support the use of SGLT2 inhibitors for the treatment of patients with heart failure and a reduced ejection fraction, regardless of the presence or absence of diabetes.”
BackgroundVascular and metabolic effects of SGLT2i and GLP-1 in heart failure patients
Correale, M., Lamacchia, O., Ciccarelli, M., Dattilo, G., Tricarico, L., & Brunetti, N. D. (2021) · Heart Failure Reviews · doi:10.1007/s10741-021-10157-y · Cited by 29
Ilyas, F., Jones, L., Tee, S. L., Horsfall, M. J., Swan, A., Wollaston, F., Hecker, T., Pasquale, C. D., Thomas, S., Chong, W., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13553 · Cited by 29
Beneš, J., Kotrč, M., Kroupova, K., Wohlfahrt, P., Kovar, J., Franeková, J., Hegarová, M., Hošková, L., Hošková, E., Pelikánová, T., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-17327-4 · Cited by 31
Use of Glucose-Lowering Agents in Diabetes and CKD
Alicic, R. Z., Neumiller, J. J., Galindo, R. J., & Tuttle, K. R. (2022) · Kidney International Reports · doi:10.1016/j.ekir.2022.09.018 · Cited by 35
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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