Optimal Uptake of SGLT2 Inhibitors Could Prevent or Postpone 7 Million Heart Failure Events Over 3 Years

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Using data from 4 major phase 3 trials and the Global Burden of Disease Report, investigators detail the potential impact of optimal prescription of SGLT2 inhibitors in heart failure by estimating the number of worsening heart failure events and cardiovascular deaths prevented or postponed as a result of uptake.

A study examining the global impact of SGLT2 inhibitor implementation in heart failure is offering clinicians insight into the potential impact of optimal uptake of the class, with estimates of a global patient population exceeding 49 million based on contemporary data.

A decision analytical study performed using data from the Global Burden of Disease (GBD) 2017 report, results indicate more than 49 million patients worldwide would be eligible for SGLT2 inhibitors and optimal uptake across the spectrum of ejection fraction would could prevent or postpone between 7-8 million total worsening heart failure events and cardiovascular deaths during a 3-year period.1

"Although new breakthrough therapies like SGLT2i are a critical advance for the heart failure field, the next critical goal must be implementation. With all the progress we have made with new effective therapies, the opportunity cost of not implementing best therapy has never been higher,” said Steve Greene, MD, assistant professor in the Division of Cardiology at Duke University School of Medicine in a statement to HCPLive.

As a result of their rapid ascent from antihyperglycemic agent to being triple indicated for diabetes, chronic kidney disease and heart failure, SGLT2 inhibitors have captured the attention of specialists throughout the cardiometabolic health community. Despite being in the spotlight, optimal implementation and prescription of the class has remained a challenge.

In the current study, Greene and an international team of investigators sought to examine the potential global impact of implementation across the spectrum of left ventricular ejection fraction (LVEF). Pooling data from 195 countries between 1990 and 2017, the GBD 2017 report provided investigators with estimates of the global prevalence of heart failure.1

Launched in 1990, the GBD contains information related to more than 350 different diseases and injuries from 195 countries. With more than 7000 contributors, the report has been cited in more than 400 publications since 2010 and generated more than 1 billion data points in 2022.2

For the purpose of analysis, investigators used the National Health and Nutrition Examination Survey to ascertain an SGLT2 inhibitor-eligible population and mapped this onto global LVEF distribution from the REPORT-HF registry. Investigators obtained the number needed to treat for 3 years for a composite of worsening heart failure events and cardiovascular deaths from estimated event rates within the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-[HEART FAILURE], and DELIVER trials and projected them onto the eligible population.1

Overall, investigators determined an estimated 49,329,000 (95% confidence interval [CI], 43,882,000-54,929,000) heart failure patients would be eligible for SGLT2 inhibitors. This group included an estimated 25,651,000 (95% CI, 22,818,000-28,563,000) with an ejection fraction of 40% or less and 23,678,000 (95% CI, 21,063,000-26,366,000) with an ejection fraction greater than 40%.1

When applying treatment effect estimates from the aforementioned trials, investigators determined optimal implementation was projected to prevent or postpone between 4,512,011 (95% CI, 4,013,686-5,024,232) to 5,986,943 (95% CI, 5,325,721-6,666,604) total worsening heart failure events and cardiovascular deaths over 3 years in those with an LVEF equal to or less than 40%. Among those with an ejection fraction greater than 40%, results indicated optimal implementation could prevent or postpone an additional 2,102,606 (95% CI, 1,870,394-2,341,301) to 2,557,224 (95% CI, 2,274,804-2,847,528) events.1

In analyses of all eligible patients, regardless of ejection fraction, investigators determined optimal implementation could prevent or postpone 7,069,235 (95% CI, 6,288,490-7,871,760) to 8,089,549 (95% CI, 7,196,115-9,007,905) total worsening heart failure events and cardiovascular deaths during a 3-year period.1

“There is a growing divide between what is possible, and what is being done in real-world practice. This analysis outlines the magnitude of this opportunity cost on a global scale for SGLT2i therapy. Optimal global implementation of SGLT2i therapy for [heart failure] would be expected to prevent 7-8 million cardiovascular deaths or worsening [heart failure] events over 3 years,” Greene added.


  1. Talha KM, Butler J, Greene SJ, et al. Potential Global Impact of Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure [published online ahead of print, 2023 Apr 16]. Eur J Heart Fail. 2023;10.1002/ej[heart failure].2864. doi:10.1002/ej[heart failure].2864
  2. Global burden of disease (GBD). Institute for Health Metrics and Evaluation. Accessed April 20, 2023.