Jardiance^® (empagliflozin) decreased relative risk of hospitalization for heart failure by 50% versus DPP-4 inhibitors and by 30% versus GLP-1 receptor agonists in adults with type 2 diabetes in real-world evidence study

INGELHEIM, GERMANY, and INDIANAPOLIS, U.S., June 6, 2022 – Two analyses of the final U.S. data from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) real-world study show that Jardiance^® (empagliflozin) was associated with a reduction in risk of hospitalization for heart failure compared with two other classes of glucose-lowering therapies in adults with type 2 diabetes in routine care.^2,3 Relative risk reductions were 50% versus dipeptidyl peptidase-4 (DPP-4) inhibitors and 30% versus glucagon-like peptide 1 (GLP-1) receptor agonists.^2,3 The results were presented on behalf of Boehringer Ingelheim and Eli Lilly and Company (NYSE:LLY) at the American Diabetes Association Scientific Sessions 2022 in New Orleans.

"Heart failure is present in up to 30% of all people with type 2 diabetes, therefore it is critical that healthcare professionals treating this population have treatments that demonstrate cardiovascular effectiveness in routine care,” said Elisabetta Patorno, M.D., Dr.P.H., Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Associate Professor of Medicine, Harvard Medical School, and study co-investigator. “These five-year results from EMPRISE, showing empagliflozin was associated with a decreased risk of hospitalization for heart failure and for death, are encouraging data for adults with type 2 diabetes and their care team.”

Compared with DPP-4 inhibitors, empagliflozin was also associated with a 40% reduction in relative risk of all-cause mortality in people who had Medicare. In the overall EMPRISE population, empagliflozin was associated with a 12% reduction in the risk of composite outcome of myocardial infarction or stroke compared with DPP-4 inhibitors.³

Compared with GLP-1 receptor agonists, empagliflozin was associated with similar risks of heart attack, stroke and all-cause mortality. All results for empagliflozin compared with GLP-1 receptor agonists, and with liraglutide (a GLP-1 receptor agonist) specifically, were consistent for people with and without cardiovascular disease.² 

Results from the EMPRISE real-world study, which assessed the first five years of use of empagliflozin in the U.S., complement previously reported data from the landmark EMPA-REG OUTCOME® trial, in which empagliflozin showed a 35% relative risk reduction in hospitalization for heart failure compared with placebo in adults with type 2 diabetes and established cardiovascular disease. EMPA-REG OUTCOME also showed a 38% relative risk reduction in cardiovascular death with empagliflozin versus placebo.^1,4

“Hospitalization for heart failure has a very real impact on the quality of life and repeated hospitalizations also translate to poorer overall outcomes,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. "We are delighted that this analysis from EMPRISE has highlighted that Jardiance, compared with other medicines, can reduce the need for hospitalization with heart failure, as well as overall deaths in people with type 2 diabetes. This is welcome data for the 60 million people living with cardio-metabolic conditions globally."

The EMPRISE findings confirmed the well-established safety profile of empagliflozin. Compared with DPP-4 inhibitors, empagliflozin was associated with a reduction in relative risk of acute kidney injury. There was an  increase in relative risk of hospitalization for diabetic ketoacidosis, which is consistent with empagliflozin’s known safety information. Risks for lower-limb amputations, fractures and renal and bladder cancers were similar.^2,3

“We are pleased to present the final data from EMPRISE in the U.S., which encompasses information from nearly 500,000 adults in a real-world care setting,” said Leonard Glass, M.D., F.A.C.E., vice president of Diabetes Global Medical Affairs, Lilly. “As we strive to help fill unmet treatment needs, this study reinforces our longstanding commitment to people living with cardio-metabolic conditions. Building upon our robust clinical trial program, EMPRISE highlights the potential of Jardiance to improve health outcomes in routine clinical practice.”  

About EMPRISE 
EMPRISE was initiated in 2016 to complement the EMPA-REG OUTCOME trial results by providing data on the comparative effectiveness and safety of Jardiance in routine clinical care versus DPP-4 inhibitors or GLP-1 receptor agonists.⁴

The final analyses of EMPRISE U.S. data assessed the first five years of Jardiance use in nearly 500,000 adults with type 2 diabetes, with and without cardiovascular disease, in the U.S. between 2014 and 2019: the first included more than 230,000 adults who initiated either Jardiance or a DPP-4 inhibitor (115,116 adults in each treatment arm); the second included more than 260,000 adults who initiated either Jardiance or a GLP-1 receptor agonist (130,408 adults in each treatment arm).^2,3

Additional EMPRISE studies including Asia and Europe will provide insights from different regions of the world with an international perspective on the use of Jardiance in routine clinical care.

EMPRISE U.S. was initiated and led by academic researchers from the Division of Pharmacoepidemiology at Brigham and Women’s Hospital and Harvard Medical School, Boston. The study is part of an academic collaboration between Brigham and Women’s Hospital and Boehringer Ingelheim.

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.^5,6 It is a widespread condition affecting over 15 million people in Europe and over 60 million people worldwide and expected to increase as the population ages.^7,8 Heart failure is highly prevalent in people with diabetes; however, approximately half of all people with heart failure do not have diabetes.^9,10

About cardio-renal-metabolic conditions
Through research and educational initiatives, Boehringer Ingelheim and Lilly are driven to redefine 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. 

The cardiovascular, renal (kidney) and metabolic systems are closely intertwined and share many of the same disease-related pathways. Dysfunction in one system may accelerate the onset of dysfunction in others, resulting in the progression of comorbid diseases such as type 2 diabetes, heart failure and chronic kidney disease. Conversely, improving the health of one system can lead to positive effects across the others and can help reduce the risk for further complications.^11,12,13

Understanding their interconnected nature, we are working to advance treatments for people with cardio-renal-metabolic conditions. It is only through a holistic approach to care that we can truly transform outcomes and restore the harmony among these critical systems.

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.^14,15

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 several 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 unites caring with discovery to create medicines that make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer’s disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn.

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 Jardiance as a treatment for adults with type 2 diabetes, to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, and as a potential treatment for adults with cardio-renal-metabolic conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date or that Jardiance will receive additional regulatory approvals. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

Contacts

Dr. Julia Faaß
Boehringer Ingelheim 
Email: press@boehringer-ingelheim.com 
Phone: +49 (6132) 77-95614

Stephan Thalen 
Global Business Communications
Lilly Diabetes and Lilly USA, LLC
Email: stephan.thalen@lilly.com  
Phone: +1 (317) 903-5640

References

¹  Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type ² Diabetes. N Engl J Med. 2015;373(22): 2117-2128
2 Htoo PT et al. Cardiovascular effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists or liraglutide in the EMPRISE study. Presented at the American Diabetes Association Scientific Sessions 2022; 5 June 2022. 1079-P.
³ Htoo PT et al. Effectiveness and safety of empagliflozin in routine care: Results from the EMPagliflozin compaRative effectiveness and SafEty (EMPRISE) study. Presented at the American Diabetes Association Scientific Sessions 2022; 4 June 2022. 179-O.
⁴  Patorno E, Najafzadeh M, Pawar A, 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. 2020;3:e00103.
⁵  American Heart Association. What is Heart Failure? Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure. Accessed: November 2021.
⁶  American Heart Association. Types of Heart Failure. Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Accessed: November 2021.
⁷  Andersen MJ, Borlaug BA. Heart failure with preserved ejection fraction: current understandings and challenges. Curr Cardiol Rep. 2014;16(7):501.
⁸  European Heart Network. Heart Failure and Cardiovascular Diseases – A European Heart Network Paper. April 2019.
⁹  Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121–41.
¹⁰ Dunlay SM, Givertz MM, Aguilar D, et al. Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America. Circulation. 2019;140:e294–e324.
¹¹ Thomas M, Cooper M, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2015;12:73–81.
¹² García-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the Cardiorenal Continuum. Int J Nephrol. 2011;2011:975782.
¹³ Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246–58.
¹⁴ 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.  Last accessed: June 2022.
¹⁵ Jardiance^® (empagliflozin) tablets, U.S. Prescribing Information. Available at: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf. Last accessed: June 2022.