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CARDIOVASCULAR PREVENTION / RESEARCH LETTER
Clinical Outcomes Following GLP-1 Receptor Agonist Initiation With Versus Without Background SGLT2 Inhibitor Therapy in Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes: A Propensity-Matched Real-World Analysis
1
Endeavor Health Cardiovascular Institute, Glenview, Illinois, United States, United States
2
Medical University of Lodz, Lodz, Poland, Poland
3
Maimonides Medical Center, 4802 10th Ave, Brooklyn, NY 11219, United States, United States
4
SUNY Upstate Medical University, Syracuse, NY, United States, United States
5
ESIC Medical College and PGIMSR, Chennai, Tamil Nadu, India, United States
6
Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Lodz, Poland;
Department of Cardiology and Congenital Heart Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland, Poland
Submission date: 2026-10-30
Acceptance date: 2026-10-31
Online publication date: 2026-11-06
Corresponding author
Agata Magdalena Bielecka-Dabrowa
Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Lodz, Poland; Department of Cardiology and Congenital Heart Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland, Poland
Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Lodz, Poland; Department of Cardiology and Congenital Heart Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
SGLT2 inhibitors (SGLT2i) improve heart failure outcomes, and GLP-1 receptor agonists (GLP-1 RA) confer cardiometabolic benefit. However, outcomes after GLP-1 RA initiation according to background SGLT2i use remain uncertain.
Material and Methods:
Using TriNetX, we compared GLP-1 RA initiation in patients with HFpEF and type 2 diabetes with versus without background SGLT2i. Cohorts were propensity-matched 1:1 and followed for one year, with 60-day landmark analyses.
Results:
Among 27,988 matched pairs, background SGLT2i was associated with lower one-year all-cause mortality (HR 0.66, 95% CI 0.61–0.71) and major adverse cardiovascular events (MACE; HR 0.78, 95% CI 0.73–0.84; both P < 0.001). Landmark analyses were consistent for ACM (HR 0.68, 95% CI 0.63–0.75) and MACE (HR 0.83, 95% CI 0.77–0.91).
Conclusions:
In HFpEF with type 2 diabetes, GLP-1 RA initiation on a background of SGLT2i therapy was associated with lower mortality and MACE than initiation without SGLT2i.
SGLT2 inhibitors (SGLT2i) improve heart failure outcomes, and GLP-1 receptor agonists (GLP-1 RA) confer cardiometabolic benefit. However, outcomes after GLP-1 RA initiation according to background SGLT2i use remain uncertain.
Material and Methods:
Using TriNetX, we compared GLP-1 RA initiation in patients with HFpEF and type 2 diabetes with versus without background SGLT2i. Cohorts were propensity-matched 1:1 and followed for one year, with 60-day landmark analyses.
Results:
Among 27,988 matched pairs, background SGLT2i was associated with lower one-year all-cause mortality (HR 0.66, 95% CI 0.61–0.71) and major adverse cardiovascular events (MACE; HR 0.78, 95% CI 0.73–0.84; both P < 0.001). Landmark analyses were consistent for ACM (HR 0.68, 95% CI 0.63–0.75) and MACE (HR 0.83, 95% CI 0.77–0.91).
Conclusions:
In HFpEF with type 2 diabetes, GLP-1 RA initiation on a background of SGLT2i therapy was associated with lower mortality and MACE than initiation without SGLT2i.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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