Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction
Open accessAbstract
Background: No study has compared the cardiovascular outcomes for sodium–glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)—which also have cardiovascular benefits—in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Methods: Medicare fee-for-service data (2013–2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. Results: Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. Conclusions: Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.
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SGLT2is and GLP-1RAs have demonstrated benefits in preventing deleterious cardiorenal endpoints among individuals with type 2 diabetes.
“In recent years, sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) have demonstrated benefits in preventing deleterious cardiorenal endpoints among individuals with type 2 diabetes, shifting disease management from a glucocentric approach to one that prioritises long-term cardiorenal health [5–7].”
From Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013–2019 (2025) · cites this paper as [7]
The Introduction (page not provided) reports cardiovascular benefits of both drug classes, and the Results report lower heart-failure hospitalization risk with SGLT2 inhibitors in older adults with type 2 diabetes and heart failure. The paper does not report prevention of renal endpoints; its own study population is also narrower than people with type 2 diabetes generally. (LLM, conf=0.86)
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- Authors
- Gonzalez, J., Bates, B. A., Setoguchi, S., Gerhard, T., & Dave, C. V.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Dave, Chintan V.
- Venue
- Cardiovascular Diabetology
- Published
- 2023-03-10
- Volume
- 22
- Issue
- 1
- Pages
- 54-54
- ISSN
- 1475-2840 (ISSN-L)
- PMC
- PMC9999503
- OpenAlex
- W4323920855
- Cited by
- 32
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 17 · 2023: 6
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cardiovascular Diabetology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (R01HL163163)
- National Institute of Environmental Health Sciences (P30ES005022)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- SGLT2 inhibitors, DPP-4 inhibitors, GLP-1 receptor agonists, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, type 2 diabetes, heart failure hospitalization, myocardial infarction, stroke, cardiovascular outcomes, glucose-lowering therapy, fee-for-service Medicare, inverse probability of treatment weighting, head-to-head comparison, real-world evidence
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Medicare, Heart Failure, Humans, Hypoglycemic Agents, Myocardial Infarction, Stroke Volume, United States, Stroke, Dipeptidyl-Peptidase IV Inhibitors
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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