SGLT2 Inhibitors and GDMT Affordably Reduce Heart Failure Mortality and Hospitalization

The use of guideline-directed medical therapy (GDMT) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with reduced total health care costs, as well as a lower risk of all-cause and heart failure (HF)-related hospitalization and all-cause mortality among patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), according to data presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025.1

Previous trials have investigated the cost-effectiveness of SGLT2is in a US patient population, highlighting the addition of empagliflozin and other similar drugs to standard-of-care treatments. These studies corroborate this new data, indicating a substantial reduction in HF-related hospitalization and mortality, as well as additional life years and quality-of-living improvements at a modest cost increase.2

“As SGLT2is are now considered a core component of GDMT, understanding the uptake and economic impact of current GDMT, including SGLT2is, in real-world practice is critical,” wrote Kaiwen Guo, MPA, Boehringer Ingelheim Pharmaceuticals, and colleagues.1

Guo and colleagues collected data on US adults recently diagnosed with HFrEF or HFpEF from the Optum Clinformatics Data Mart (CDM) database. For inclusion in the study, patients had to have ≥1 inpatient or ≥2 outpatient diagnosis codes, as well as ≥12 months of continuous enrollment +/- index, no prior HF diagnosis 12 months before index, ≥30 days follow-up after index, and not both HFpEF and HFrEF present at index.1

Investigators identified 14,523 patients with HFrEF (mean age, 74 years; 58.5% male) and 21,535 with HFpEF (mean age, 77 years; 41.2% male). Patients contributed 26,447 HFrEF treatment episodes and 24,632 HFpEF treatment episodes. In HFrEF, treatment episodes were categorized as GDMT (n=1,057), incomplete GDMT with SGLT2i (n=3,751), incomplete GDMT without SGLT2i (n=12,675), and no GDMT (n=8,964). For HFpEF, episodes were defined as SGLT2i (n=2,980) or no SGLT2i (n=21,652).1

Within 12 months of diagnosis, only 5.3% of patients with HFrEF initiated ≥1 GDMT episode, while 21.0% of HFrEF and 10.3% of HFpEF patients received ≥1 SGLT2i episode.1

Economic outcomes varied substantially. Among HFrEF episodes, mean per-person-per-month (PPPM) costs were $14,128.80 for GDMT, $16,449.00 for incomplete GDMT with SGLT2i, $21,887.20 for incomplete GDMT without SGLT2i, and $28,232.30 for no GDMT. In HFpEF episodes, PPPM costs were $16,136.70 with SGLT2i versus $22,745.70 without.1

Clinical outcomes reflected similar trends. HF-related inpatient admissions or death per 1,000 person-months were lowest in HFrEF episodes with GDMT (41.5), compared with incomplete GDMT with SGLT2i (66.8), incomplete GDMT without SGLT2i (98.0), and no GDMT (140.1). Among HFpEF episodes, rates were 73.3 with SGLT2i versus 134.6 without.1

Ultimately, investigators believe the use of GDMT and SGLT2is is associated with an overall reduction in total health care costs, as well as a reduction in all-cause mortality, all-cause hospitalization, and HF-related hospitalization in patients.1

“Despite guideline recommendations and the demonstrated benefits, the uptake of GDMT and SGLT2is within the first year of diagnosis remains suboptimal,” Guo and colleagues wrote. “Improving the adoption of GDMT could translate into substantial reductions in both clinical and economic burden.”1

References

1. Guo K. Clinical and Economic Benefit of GDMT and SGLT2i Among US Adults with Newly Diagnosed HFrEF and HFpEF. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

2. Reifsnider OS, Tafazzoli A, Linden S, et al. Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States. J Am Heart Assoc. 2024;13(4):e029042. doi:10.1161/JAHA.123.029042