“Will we see progressive providers prescribing ‘ahead’ of guidelines? Maybe. A recent JACC editorial suggests that SGLT2is and GLP-1 RAs should be considered standard of care for high-risk individuals, given the clear benefits of each drug via distinct pathways. That said, the majority of patients who could benefit from either (or both) of these therapies are not getting them – highlighting the need for additional data and tools that could influence practice patterns.”
Kahla Verhoef
Chief Operating Officer, egnite
Heart failure with a preserved ejection fraction (HFpEF) accounts for more than half of all heart failure cases and carries significant morbidity and mortality risk, especially after hospitalization1. Historically, management of the disease is largely focused on comorbidity management and lifestyle modifications, given that available therapies had not demonstrated sufficient impact on hospitalization burden or mortality. In recent years, however, the treatment paradigm for HFpEF has shifted, with a growing emphasis on SGLT2 inhibitors (SGLT2i). Originally developed to lower blood glucose levels in diabetic patients, several clinical trials have firmly established that SGLT2i is also beneficial for patients living with HFpEF2.
In addition to SGLT2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging as potentially beneficial adjuncts. Recent evidence suggests that GLP-1 RAs may be an effective therapy to promote weight loss and symptom improvement in HFpEF3, and a newly published analysis from the SUMMIT trial demonstrated that use of a GLP-1 RA in patients with HFpEF and obesity lowered the risk for cardiovascular events4. Interest in GLP-1 RAs as an additive therapy for HFpEF patients has piqued recently given the significant amount of HFpEF patients with obesity and/or diabetes (up to 84% and 45% respectively)5,6. To date, however, this exploration has been largely limited by the low use of SGLT2is in GLP-1 RA trials.
Fortunately, we have a lot of data at egnite (120,000+ HFpEF patients with documented EFs and a HF hospitalization!). We leveraged our combined echo and EMR data to explore real world practice patterns for SGLT2is and GLP-1 RAs in the HFpEF population. While recent analyses have focused on the additive benefits of GLP-1 RA in HFpEF patients with obesity and type 2 diabetes, our data suggest there could be benefits within a broader HFpEF population in utilizing GLP-1 RAs alone and in combination with SGLT2is7. Read more below!
Real-World Data for HFpEF Patients
Given the particularly poor prognosis of HFpEF patients post HF-related hospitalization, we analyzed a real-world cohort of 122,008 patients with a HFpEF diagnosis and a subsequent HF admission to understand prescription rates pre and post hospitalization (index event), as well as resulting mortality rates. Patients were stratified by SGLT2i and GLP-1 RA prescriptions at their index hospitalization, with a time-varying Kaplan–Meier approach accounting for treatment changes if additional prescriptions were initiated post-index. Trends in prescribing patterns were assessed by tracking the proportion of HFpEF patients prescribed GLP-1 RA and/or SGLT2i at the time of HF admission.
Observed Mortality Stratified by GLP-1 RA and/or SGLT2i Prescription
Estimated 2-year mortality rates were lowest for HFpEF patients prescribed both a GLP-1 RA and SGLT2i (13.1%), followed by those that were prescribed a GLP-1 RA only (17.8%) or an SGLT2i only (20.6%). Lack of either prescription was associated with the highest two-year mortality rate (28.1%), highlighting a gap in the treatment of HFpEF patients given the number of patients that fall into this cohort.
Real-World Data: GLP-1 RA and SGLT2i Prescription Rates at HF Admission
While prescription rates for both SGLT2i and GLP-1 RAs have risen since 2018, the prescription rates for SGLT2is remain surprisingly low given that current guidelines suggest SGLT2i’s should be initiated in all individuals with HFpEF unless contraindicated8. As of December 2024, 18.7% of HFpEF patients were prescribed a SGLT2i only, 13.6% GLP-1 RA only, 6.3% were prescribed both and 74% remained without a prescription for GLP-1 RAs or SGLT2i.
Real-World Practice Considerations
Our findings are broadly consistent with numerous studies that point to the underutilization of SGLT2 inhibitors9 in practice. In STEP-HFpEF DM, for example, less than one third of patients with HFpEF, obesity, and type two diabetes were on an SGLT2 inhibitor at baseline. In a recent publication examining real world prescription trends for SGLT2is, a mere 3.1% of patients with a Class 1a recommendation for SGLT2i were prescribed across 28 health systems10. Roadblocks further downstream, such as limited insurance coverage and high out of pocket costs, could further inhibit utilization even if providers enhance their prescription rates.
While limited in the context of HFpEF, GLP-1 RAs have also seen a low uptake in the eligible population(s) for which they are indicated11 primarily due to high costs and accessibility12. As additional applications and potential additive benefits of GLP1 RAs for different disease states, such as HFpEF, are further explored, we may continue to see limited positive outcomes in these vulnerable patient populations if these broader concerns surrounding cost and patient access are not addressed.
Future Direction & Unanswered Questions
Could we see GLP-1 RAs introduced as a recommended drug for HFpEF patients in the guidelines? The 2023 Expert Consensus Decision Pathway on Management of HFpEF points to the possibility,
highlighting the utility of GLP-1 RAs in HFpEF patients with obesity.
Will we see progressive providers prescribing ‘ahead’ of guidelines? Maybe. A recent JACC editorial suggests that SGLT2is and GLP-1 RAs should be considered standard of care for high risk individuals, given the clear benefits of each drug via distinct pathways13. That said, the majority of patients who could benefit from either (or both) of these therapies are not getting them – highlighting the need for additional data and tools that could influence practice patterns.
While the clinical community is waiting on randomized trials to demonstrate the long-term impact of GLP-1 RAs in HFpEF, we anticipate that real world data may play a key role in demonstrating the benefit of both GLP-1 RAs and the incremental benefit of GLP-1 RAs and SGLT2is for these patients.
Final Thoughts
egnite’s data Registry delivers a comprehensive view of cardiovascular populations, with 3x more cardiovascular patients than commonly used EHR datasets. If you’d like to talk to explore how you can leverage RWD within your organization, please reach out to christopher.edie@egnitehealth.com.
References
- Carson, P, Anand, I, Win, S. et al. The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart Failure With Preserved Ejection Fraction: Results From the I-PRESERVE Trial (Irbesartan in Heart Failure and Preserved Ejection Fraction). J Am Coll Cardiol HF. 2015 Jun, 3 (6) 429–441. https://doi.org/10.1016/j.jchf.2014.12.017
- Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomized controlled trials. Lancet. 2022;400:757–767
- Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963.
- Bosworth, Ted. New GLP-1 Data Reinforce CV Benefit. 21 Feb 2025. https://www.medscape.com/viewarticle/new-glp-1-data-reinforce-cv-benefit-2025a10004ki?form=fpf
- Prausmüller S, Weidenhammer A, Heitzinger G, et al. Obesity in heart failure with preserved ejection fraction with and without diabetes: risk factor or innocent bystander? Eur J Prev Cardiol. 2023;30(12):1247–1254. doi:10.1093/eurjpc/zwad140.
- Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2018;39(30):2580-2593. doi:10.1093/eurheartj/ehy129.
- Dobbles, Michael. Post HF Admission Mortality in HFpEF. 11 Mar 2025.
- Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(18):1835-1878. doi: 10.1016/j.jacc.2023.03.393.
- Maxwell YL. Only small minority of eligible patients prescribed SGLT2 inhibitors. 15 Aug 2024. https://www.tctmd.com/news/only-small-minority-eligible-patients-prescribed-sglt2-inhibitors
- Shin JI, Xu Y, Chang AR, Carrero JJ, Flaherty CM, Mukhopadhyay A, Inker LA, Blecker SB, Horwitz LI, Grams ME. Prescription Patterns for Sodium-Glucose Cotransporter 2 Inhibitors in U.S. Health Systems. J Am Coll Cardiol. 2024 Aug 20;84(8):683-693. doi: 10.1016/j.jacc.2024.05.057. PMID: 39142721; PMCID: PMC11789666.
- GLP-1 drugs are not specifically FDA approved for HFpEF. Depending on the drug and dose, they are currently approved for use in Type 2 diabetes or obesity.
- Higgins L. Are you eligible for Ozempic? New study suggests over half of U.S. adults qualify. com. Published November 22, 2024. Available from: https://www.health.com/ozempic-semaglutide-american-eligibility-8747341.
- Harrington et al. SGLT2 Inhibitors and GLP-1 Ras: A One-Two Punch? JACC: Heart Failure Vol. 12, No. 11, 2024. pg 1828
Bio
Kahla Verhoef is the Chief Product Officer of egnite, Inc., a leading Cardiovascular Digital Healthcare company partnered with over 55 heart programs and 400 affiliated healthcare facilities nationally.
