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SGLT2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials
Open accessAbstract
BACKGROUND: SGLT2 inhibitors are strongly recommended in guidelines to treat patients with heart failure with reduced ejection fraction, but their clinical benefits at higher ejection fractions are less well established. Two large-scale trials, DELIVER and EMPEROR-Preserved, in heart failure with mildly reduced or preserved ejection fraction have been done, providing power to examine therapeutic effects on cardiovascular mortality and in patient subgroups when combined with the earlier trials in reduced ejection fraction. METHODS: We did a prespecified meta-analysis of DELIVER and EMPEROR-Preserved, and subsequently included trials that enrolled patients with reduced ejection fraction (DAPA-HF and EMPEROR-Reduced) and those admitted to hospital with worsening heart failure, irrespective of ejection fraction (SOLOIST-WHF). Using trial-level data with harmonised endpoint definitions, we did a fixed-effects meta-analysis to estimate the effect of SGLT2 inhibitors on various clinical endpoints in heart failure The primary endpoint for this meta-analysis was time from randomisation to the occurrence of the composite of cardiovascular death or hospitalisation for heart failure. We assessed heterogeneity in treatment effects for the primary endpoint across subgroups of interest. This study is registered with PROSPERO, CRD42022327527. FINDINGS: Among 12 251 participants from DELIVER and EMPEROR-Preserved, SGLT2 inhibitors reduced composite cardiovascular death or first hospitalisation for heart failure (hazard ratio 0·80 [95% CI 0·73-0·87]) with consistent reductions in both components: cardiovascular death (0·88 [0·77-1·00]) and first hospitalisation for heart failure (0·74 [0·67-0·83]). In the broader context of the five trials of 21 947 participants, SGLT2 inhibitors reduced the risk of composite cardiovascular death or hospitalisation for heart failure (0·77 [0·72-0·82]), cardiovascular death (0·87 [0·79-0·95]), first hospitalisation for heart failure (0·72 [0·67-0·78]), and all-cause mortality (0·92 [0·86-0·99]). These treatment effects for each of the studied endpoints were consistently observed in both the trials of heart failure with mildly reduced or preserved ejection fraction and across all five trials. Treatment effects on the primary endpoint were generally consistent across the 14 subgroups examined, including ejection fraction. INTERPRETATION: SGLT2 inhibitors reduced the risk of cardiovascular death and hospitalisations for heart failure in a broad range of patients with heart failure, supporting their role as a foundational therapy for heart failure, irrespective of ejection fraction or care setting. FUNDING: None.
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“These drug classes are recommended as glucose-lowering therapy for individuals with cardiovascular disease or risk factors6,7 on the basis of randomized clinical trial evidence demonstrating a reduction in cardiovascular events (SGLT2is and GLP-1RAs)14,15,16 or suggesting cardiovascular benefit (metformin and pioglitazone).17,18”
From Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis (2025) · cites this paper as [15]
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
“Large placebo-controlled trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of cardiovascular disease, and particularly hospitalisation for heart failure, in patients with type 2 diabetes at high risk of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease.”
From Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials (2022) · cites this paper as [5]
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In the citing paper
“a large meta-analysis (308) including the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trials included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death,”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [308]
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“A large meta-analysis (297) including the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and SOLOIST-WHF trials included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death, first hospitalization for heart failure, and all-cause mortality.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [297]
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“The findings on the studied end points were consistent in both trials of heart failure with mildly reduced or preserved ejection fraction and in all five trials combined.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [297]
In the citing paper
“Over the past decade, several large RCTs failed to achieve statistical significance with regard to effects on the primary outcomes in patients with HFpEF including: PEP-CHF (perindopril), CHARM-Preserved (candesartan), I-PRESERVE (irbesartan), TOPCAT (spironolactone), DIG Ancillary Trial (digoxin), and PARAGON-HF (sacubitril/valsartan). 477,[534][535][536][537][538]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [535]
In the citing paper
“There is good evidence to support the use of SGLT2 inhibitors as a foundational therapy to prevent cardiovascular death or hospitalisation for heart failure in patients with heart failure, irrespective of ejection fraction or history of previous diabetes.1, 2, 3, 4, 5”
In the citing paper
“A large recent meta-analysis (227) including data from EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and Effect of Sotagli fl ozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOISTWHF) included 21,947 patients and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death, fi r”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [227]
In the citing paper
“The fi ndings on the studied end points were consistent in both trials of heart failure with mildly reduced or preserved ejection fraction and in all fi ve trials combined.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [227]
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Citations
Cites
2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344
Self-citationDapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
McMurray, J. J. V., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Anand, I. S., Bělohlávek, J., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1911303 · Cited by 7,140
Self-citationCardiovascular and renal outcomes with empagliflozin in heart failure
Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022190 · Cited by 5,206
Empagliflozin in heart failure with a preserved ejection fraction
Anker, S. D., Butler, J., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., Brunner–La Rocca, H.-P., Choi, D.-J., Chopra, V., Chuquiure-Valenzuela, E., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107038 · Cited by 4,874
Self-citationDapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction
Solomon, S. D., McMurray, J. J. V., Claggett, B., de Boer, R. A., DeMets, D., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Martinez, F., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206286 · Cited by 2,884
Self-citationSotagliflozin in patients with diabetes and recent worsening heart failure
Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., Lewis, J. B., Riddle, M. C., Voors, A. A., Metra, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2030183 · Cited by 1,868
Zannad, F., Ferreira, J. P., Pocock, S. J., Anker, S. D., Butler, J., Filippatos, G., Brueckmann, M., Ofstad, A. P., Pfarr, E., Jamal, W., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31824-9 · Cited by 1,408
McGuire, D. K., Shih, W. J., Cosentino, F., Charbonnel, B., Cherney, D. Z. I., Dagogo-Jack, S., Pratley, R., Greenberg, M., Wang, S., Huyck, S., et al. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2020.4511 · Cited by 1,235
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.011 · Cited by 931
Self-citationSolomon, S. D., Anavekar, N. S., Skali, H., McMurray, J. J. V., Swedberg, K. B., Yusuf, S., Granger, C. B., Michelson, E. L., Wang, D., Pocock, S., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.561423 · Cited by 873
Self-citationCalculating the number needed to treat for trials where the outcome is time to an event
Altman, D. G., & Andersen, P. K. (1999) · BMJ · doi:10.1136/bmj.319.7223.1492 · Cited by 710
Nassif, M. E., Windsor, S. L., Borlaug, B. A., Kitzman, D. W., Shah, S. J., Tang, F., Khariton, Y., Malik, A. O., Khumri, T., Umpierrez, G., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01536-x · Cited by 618
Self-citationSacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure
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Packer, M., Butler, J., Zannad, F. M., Filippatos, G. S., Ferreira, J. P., Pocock, S., Carson, P. E., Anand, I. S., Doehner, W., Haass, M., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.056824 · Cited by 368
Butler, J., Packer, M., Filippatos, G., Ferreira, J. P., Zeller, C., Schnee, J., Brueckmann, M., Pocock, S. J., Zannad, F., & Anker, S. D. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehab798 · Cited by 264
Spertus, J. A., Birmingham, M. C., Nassif, M., Damaraju, C. V., Abbate, A., Butler, J., Lanfear, D. E., Lingvay, I., Kosiborod, M. N., & Januzzi, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01703-8 · Cited by 245
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Research works printed but not linked: 1
- Zannad, 2020, SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials, Lancet, 396, 819, 10.1016/S0140-6736(20)31824-9 · DOI · Paper page
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Self-citation2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
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Metadata
- Authors
- Vaduganathan, M., Docherty, K. F., Claggett, B. L., Jhund, P. S., de Boer, R. A., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Martinez, F., Shah, S. J., Desai, A. S., McMurray, J. J. V., & Solomon, S. D.
- Affiliations
- Brigham and Women's Hospital (US)
- British Heart Foundation (GB)
- Duke Medical Center (US)
- Yale University (US)
- University of Missouri–Kansas City (US)
- National University of Singapore (SG)
- Northwestern University (US)
- Corresponding author
- Solomon, Scott D
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 400
- Issue
- 10354
- Pages
- 757-767
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W4293353625
- Cited by
- 996
- References
- 24
- Citations by year
- 2026: 215 · 2025: 203 · 2024: 279 · 2023: 257 · 2022: 42
- FWCI
- 39.76
- Type
- journal article
- Language
- en
- Update notices
- erratum (2023-01-14)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion, public-domain)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, public-domain)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, public-domain)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Amgen
- Eli Lilly and Company (NCT03057951)
- Pfizer
- AstraZeneca
- Sanofi
- National Institutes of Health
- Defense Acquisition Program Administration
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- SGLT2 inhibitors, heart failure, heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, cardiovascular mortality, heart failure hospitalization, all-cause mortality, subgroup analysis, DAPA-HF, EMPEROR-Preserved, EMPEROR-Reduced, cardiovascular risk stratification, treatment effect heterogeneity
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Heart Failure, Hospitalization, Humans, Stroke Volume, Randomized Controlled Trials as Topic, Ventricular Function, Left, Ventricular Dysfunction, Left
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