In 141,541 matched patient pairs, empagliflozin was associated with a 50% lower risk of heart failure hospitalization and 25% lower risk of kidney disease progression compared to GLP-1 receptor agonists, with similar rates of heart attack and stroke.
HR 0.50 for heart failureEmpagliflozin halved the risk of heart failure hospitalization compared to GLP-1 receptor agonists in 141,541 matched patient pairs
What the researchers found
Compared with GLP-1 receptor agonists, empagliflozin was associated with:
- Similar risk of MI or stroke: HR 0.99 (95% CI: 0.92-1.07)
- 50% lower risk of heart failure hospitalization: HR 0.50 (0.44-0.56)
- 10% lower risk of MACE: HR 0.90 (0.82-0.99)
- 23% lower risk of CV mortality or HHF composite: HR 0.77 (0.69-0.86)
- 25% lower risk of progression to ESKD in CKD stage 3-4 patients: HR 0.75 (0.60-0.94)
Absolute risk reductions were larger in older patients and those with baseline ASCVD or heart failure. Benefits did not differ by sex.
Why it matters
Clinicians treating type 2 diabetes must choose between SGLT-2 inhibitors and GLP-1 peptide agonists — both of which have cardiovascular benefits. Without head-to-head randomized trials, real-world evidence like EMPRISE fills a critical gap. These results suggest empagliflozin may be preferable for patients at high risk of heart failure or kidney disease, while GLP-1 agonists perform comparably for atherosclerotic events like heart attack and stroke. This informs personalized drug selection for millions of diabetes patients.
How the study worked
Retrospective propensity score-matched cohort study using US Medicare and commercial claims databases (2014-2019). 141,541 pairs of patients ≥18 years with type 2 diabetes who initiated empagliflozin or a GLP-1 RA were matched 1:1 using 143 baseline characteristics. Outcomes were evaluated using hazard ratios and rate differences per 1,000 person-years. Subgroup analyses examined effects by age, sex, baseline ASCVD, and heart failure history.
What this study cannot tell us
This is an observational study using claims data, not a randomized trial, so residual confounding cannot be entirely eliminated despite matching on 143 variables. Claims data may misclassify outcomes or miss events not captured in billing records. The GLP-1 RA group included multiple agents (with varying efficacy), rather than comparing empagliflozin to a single GLP-1 RA. The study period (2014-2019) predates the widespread use of higher-dose semaglutide and tirzepatide. Cardiovascular mortality was identified from claims data, which has known limitations.
How to read the evidence
This is a large, well-designed propensity score-matched observational study using real-world data from over 283,000 patients. The 143-variable matching is rigorous, but it remains observational — a randomized trial would provide stronger causal evidence.
When this study was published
Published in 2024 as the final-year results of the EMPRISE monitoring program (2014-2019 data). While the study period predates newer GLP-1 agents, the scale and rigor of the comparison remain highly informative for current clinical practice.
The bigger picture
EMPRISE is one of the largest real-world studies comparing these two blockbuster drug classes. As GLP-1 peptide agonists dominate headlines for weight loss, this study provides important context: for heart failure and kidney protection specifically, SGLT-2 inhibitors like empagliflozin may offer superior cardiorenal benefits. This supports the emerging clinical paradigm of using both drug classes together — leveraging SGLT-2 inhibitors for heart failure and kidney protection while using GLP-1 agonists for atherosclerotic risk reduction and weight management.
Questions still open
- Would a randomized trial comparing empagliflozin to semaglutide specifically confirm the heart failure hospitalization advantage?
- Does combining empagliflozin with a GLP-1 agonist provide additive cardiorenal benefits compared to either drug alone?
- Would newer GLP-1 agonists like high-dose semaglutide or tirzepatide narrow the heart failure gap seen in this study?
Common questions
Is empagliflozin better than GLP-1 drugs for the heart?
Should diabetes patients take both types of drugs?
Read the original research
Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study.
Cardiovascular diabetology, 23(1), 57
Citation
Htoo, Phyo T; Tesfaye, Helen; Schneeweiss, Sebastian; Wexler, Deborah J; Everett, Brendan M; Glynn, Robert J; Schmedt, Niklas; Koeneman, Lisette; Déruaz-Luyet, Anouk; Paik, Julie M; Patorno, Elisabetta. (2024). Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study.. Cardiovascular diabetology, 23(1), 57. https://doi.org/10.1186/s12933-024-02150-0