Empagliflozin reduced the risk of cardiovascular events and hospitalization for heart failure compared to DPP-4 inhibitors in people with type 2 diabetes

Ingelheim, Germany and Indianapolis, US, Mon, 06/28/2021 - 10:00

Interim analysis of the EMPRISE real-world evidence study showed that empagliflozin was associated with a reduced risk in all-cause mortality, hospitalization for heart failure and acute kidney injury requiring dialysis, compared to DPP-4 inhibitors
This analysis, which includes European data pooled with data from Israel and East Asia, was presented for the first time at the American Diabetes Association Scientific Sessions, 25 June 2021¹
EMPRISE data complement the landmark EMPA-REG OUTCOME® trial

Ingelheim, Germany and Indianapolis, US, 28 June 2021 – The first data from Europe, Israel and East Asia in the EMPRISE real-world evidence study have been presented, revealing a risk reduction in cardiovascular outcomes associated with empagliflozin compared to DPP-4 inhibitors. Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced the study results today, which included over 130,000 adults with type 2 diabetes, with or without cardiovascular disease, showing a:

45 percent relative risk reduction (RRR) in all-cause mortality;
29 percent RRR in hospitalization for heart failure;
33 percent RRR in a composite endpoint including heart attack, stroke and all-cause mortality.¹

These results were consistent in people with or without cardiovascular disease. The European, Israeli and East Asian results were presented at the 81^st American Diabetes Association (ADA) Scientific Sessions, with further European analyses to be revealed at the European Society of Cardiology (ESC) Heart Failure Congress in June–July 2021, and the ESC Congress in August 2021.

The EMPRISE findings confirmed empagliflozin’s well-established safety profile. Empagliflozin was not associated with a risk of acute kidney injury - analyses showed a 51 percent RRR in acute kidney injury requiring dialysis. There was a similar risk of lower limb amputation and bone fractures as with DPP-4 inhibitors. In addition, there was an increased risk of diabetic ketoacidosis, which is consistent with empagliflozin’s known safety information.¹

“The risk of hospitalization for heart failure is up to five times higher if you have type 2 diabetes. Heart failure has a considerable impact on a person’s quality of life and prognosis, plus associated healthcare costs,” commented EMPRISE EU investigator Professor Avraham Karasik, Professor and Vice Dean, Sackler School of Medicine, Tel-Aviv University. “These latest EMPRISE findings demonstrate the impact of empagliflozin in the real-world across Europe, Israel and East Asia, supporting its role in reducing cardiovascular complications in people with type 2 diabetes.”

Type 2 diabetes significantly increases the risk of cardiovascular morbidity and mortality. One in two people with type 2 diabetes die from a cardiovascular event globally, and US data show that those with diabetes are twice as likely to develop heart failure than those without.^2,3

“The EMPRISE study evaluates extensive endpoints in a broad patient population, providing valuable insights into empagliflozin’s cardiovascular risk reduction potential in the treatment of type 2 diabetes,” said Waheed Jamal, MD, Corporate Vice President and Head of Cardiometabolic Medicine, Boehringer Ingelheim. “These results are positive and encouraging for patients, who will benefit from our continued focus on improving the outcomes for people with cardio-renal-metabolic diseases, like type 2 diabetes and heart failure.”

Findings from the EMPRISE real-world evidence study complement insights from the EMPA-REG OUTCOME^® trial, which showed that empagliflozin provides cardiovascular and renal benefits, in addition to metabolic effects, in people with type 2 diabetes and established cardiovascular disease. The EMPA-REG OUTCOME^® trial found that empagliflozin reduced the relative risk of hospitalization for heart failure by 35 percent, all-cause mortality by 32 percent and incident or worsening kidney disease by 39 percent, compared to placebo.⁴

“The evidence seen in the EMPRISE analysis provides reassurance supporting empagliflozin’s safety profile,” added Leonard Glass, Vice President of Medical Affairs, Lilly. “It is five years since the landmark EMPA-REG OUTCOME study and these latest EMPRISE findings add to the wealth of robust, real-world data demonstrating empagliflozin’s effectiveness and safety in routine clinical practice worldwide.”

About EMPRISE

The EMPRISE real-world evidence study involves nearly 382,000 people with type 2 diabetes from 12 countries providing a comprehensive clinical picture of empagliflozin in treating people with type 2 diabetes compared to DPP-4 inhibitors or GLP-1 receptor agonists (two active comparators). EMPRISE aims to assess the comparative effectiveness, safety, healthcare resource utilization and costs of care, and includes the US, Europe, Israel and East Asia.^1,5

About Cardio-Renal-Metabolic Conditions

Boehringer Ingelheim and Lilly are driven to transform care for people with cardio-renal-metabolic conditions, a group of interconnected disorders that affect more than one billion people worldwide and are a leading cause of death.⁶

The cardiovascular, renal and metabolic systems are interconnected, and share many of the same risk factors and pathological pathways along the disease continuum. Dysfunction in one system may accelerate the onset of others, resulting in progression of interconnected diseases such as type 2 diabetes, cardiovascular disease, heart failure, and kidney disease, which in turn leads to an increased risk of cardiovascular death. Conversely, improving the health of one system can lead to positive effects throughout the others.^7,8

Through our research and treatments, our goal is to support people’s health, restoring the balance between the interconnected cardio-renal-metabolic systems and reducing their risk of serious complications. As part of our commitment to those whose health is jeopardized by cardio-renal-metabolic conditions, we will continue embracing a multidisciplinary approach towards care and focusing our resources on filling treatment gaps.

About Heart Failure

Heart failure is a progressive, debilitating and potentially fatal condition that occurs when the heart cannot supply adequate circulation to meet the body’s demands for oxygenated blood, or to do so requires increased blood volume leading to fluid accumulation (congestion) in the lungs and peripheral tissues.⁹ It is a widespread condition affecting over 60 million people worldwide and expected to increase as the population ages. Heart failure is highly prevalent in people with diabetes;¹⁰ however, approximately half of all people with heart failure do not have diabetes. ¹¹

About Empagliflozin

Empagliflozin (marketed as Jardiance^®) is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in its label in several countries.^12,13,14

About the EMPOWER Program

The Alliance has developed the EMPOWER program to explore the impact of empagliflozin on major clinical cardiovascular and renal outcomes in a spectrum of cardio-renal-metabolic conditions. Cardio-renal-metabolic conditions are the leading cause of mortality worldwide and account for up to 20 million deaths annually.⁶Through the EMPOWER program, Boehringer Ingelheim and Lilly are working to advance knowledge of these interconnected systems and create care which offers integrated, multi-organ benefits. Comprised of eight clinical trials and two real-world evidence studies, EMPOWER reinforces the long-term commitment of the Alliance to improve outcomes for people living with cardio-renal-metabolic conditions. With more than 400,000 adults studied worldwide in clinical studies, it is the broadest and most comprehensive clinical program for an SGLT2 inhibitor to date.

About Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing some of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world’s leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need. Clinical trials have been initiated to evaluate the impact of empagliflozin on people living with heart failure or chronic kidney disease.

About Boehringer Ingelheim

Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com

About Eli Lilly and Company

Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom.

Intended audiences

This press release is issued from Boehringer Ingelheim Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where Boehringer Ingelheim and Eli Lilly and Company do business. This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about clinical trials to evaluate empagliflozin as a treatment for adults with heart failure and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that empagliflozin will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

CONTACTS:

Greg Kueterman

Senior Director of Communications

Eli Lilly and Company

Email: kueterman_gregory_andrew@lilly.com

Phone: +1-317-432-5195

References

¹Karasik A, et al. Effectiveness and Safety of Empagliflozin in Routine Care in Europe and East Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Study. Presented at: American Diabetes Association’s 81st Scientific Sessions; June 25-29, 2021, Washington DC, U.S.
²Einarson TR et al. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovascular Diabetology. 2018;17(83).
³Komanduri S, et al. Prevalence and risk factors of heart failure in the USA: NHANES 2013 – 2014 epidemiological follow-up study. J Community Hosp Intern Med Perspect. 2017 Jan;7(1):15–20.
⁴ Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117-28.
⁵ Patorno E, et al. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: Design and exposure accrual for an evaluation of empagliflozin in routine clinical care. Endocrinol Diab Metab. 2019;3(1):e00103.
⁶ GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016; 388(10053):1459–544.
⁷ Ronco C, McCullough P, Anker SD, et al. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Eur Heart J. 2010;31(6):703–11.
⁸ Lazzeri C, Valente S, Tarquini R, et al. Cardiorenal syndrome caused by heart failure with preserved ejection fraction. Int J Nephrol. 2011;2011:634903.
⁹ American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: June 2021.
¹⁰ Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;128(16):e240–e327.
¹¹ Suskin N, McKelvie RS, Burns RJ, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J. 2000;21:1368–75.
¹²Jardiance® (empagliflozin) tablets, U.S. Prescribing Information. Available at: https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Accessed: June 2021.
¹³ Jardiance® (empagliflozin) tablets. European Product Information; approved April 2020. Available at: https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Accessed June 2021.
¹⁴Jardiance® (Full Prescribing Information). Mexico; Boehringer Ingelheim Pharmaceuticals, Inc; 2017.