Empagliflozin reduced the risk of first plus recurrent cardiovascular events in adults with type 2 diabetes and established cardiovascular disease in new analysis from the EMPA-REG OUTCOME® trial

Ingelheim, Germany, and Indianapolis, U.S., 18 November 2020 – Empagliflozin reduced the risk of total (first plus recurrent) cardiovascular events compared with placebo, when both were given on top of standard of care, in adults with type 2 diabetes and established cardiovascular disease over the three years of the EMPA-REG OUTCOME^® trial, according to results of a new post-hoc analysis. Total cardiovascular events included 3P-MACE (a composite of non-fatal heart attack, non-fatal stroke and cardiovascular death), hospitalization for heart failure and all-cause hospitalization. The findings, announced by Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY), were published in The Lancet Diabetes & Endocrinology.²

“People with type 2 diabetes and established atherosclerotic cardiovascular disease are at an increased risk of cardiovascular complications often requiring recurrent admissions to hospital, imposing a significant burden on quality of life for patients and on healthcare systems,” said Darren McGuire, M.D., M.H.Sc., lead author of the analysis and Professor of Medicine at the University of Texas Southwestern Medical Center and Parkland Health and Hospital System. “Considering the totality of hospitalization events, as opposed to just the first event that is most commonly analyzed in clinical trials, better reflects the net effect of beneficial therapies. These new findings help us understand the impact of long-term treatment with empagliflozin for adults who may experience recurrent events due to these debilitating conditions.”

Previously, the landmark EMPA-REG OUTCOME^® trial showed that, in adults with type 2 diabetes and established cardiovascular disease, empagliflozin reduced the relative risk of 3P-MACE by 14 percent, driven by a 38 percent reduction in the relative risk of cardiovascular death.³

These new exploratory analyses show that, when added to standard of care, empagliflozin reduced the relative risk of the following total (first plus recurrent) events versus placebo:²

• 3P-MACE by 22 percent
•  Hospitalizations for heart failure by 42 percent
• All-cause hospitalizations by 17 percent
• Fatal or non-fatal myocardial infarction, commonly known as heart attack, by 21 percent
• Coronary heart disease events (a composite of myocardial infarction and coronary revascularization) by 20 percent.

“These new findings add to previous evidence of the ability of empagliflozin to reduce cardiovascular and all-cause mortality, and in fact suggest additional positive effects of empagliflozin on hospitalization and atherosclerosis-related outcomes in people with type 2 diabetes with established cardiovascular disease,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim.

“Boehringer Ingelheim and Lilly will continue to explore how empagliflozin can potentially improve health outcomes and fill treatment gaps for adults with type 2 diabetes and heart disease,” said Jeff Emmick, M.D., Ph.D., Vice President, Product Development, Lilly. “We look forward to presenting further results from our EMPOWER program, which is one of the largest cardiovascular clinical programs for an SGLT2 inhibitor to date with more than 377,000 adults studied worldwide.”

About EMPA-REG OUTCOME^® (NCT01131676)³
EMPA-REG OUTCOME^® was a long-term, multicenter, randomized, double-blind, placebo-controlled trial of more than 7,000 patients from 42 countries with type 2 diabetes and established cardiovascular disease.

The study assessed the effect of empagliflozin (10 mg or 25 mg once daily) added to standard of care compared with placebo added to standard of care. Standard of care was comprised of glucose-lowering agents and cardiovascular drugs (including medication for the treatment of hypertension and hypercholesteremia). The primary endpoint was defined as time to first occurrence of cardiovascular death, non-fatal heart attack or non-fatal stroke.

The overall safety profile of empagliflozin was consistent with that of previous trials.

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.⁴ Through 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 nine 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 377,000 adults estimated to have enrolled worldwide upon completion of the studies, it is one of the broadest and most comprehensive clinical programs for an SGLT2 inhibitor to date.

The development program encompasses:

• EMPEROR-Reduced, in adults with chronic heart failure with reduced ejection fraction to reduce the risk of cardiovascular death or hospitalization due to heart failure⁵
• EMPEROR-Preserved, in adults with chronic heart failure with preserved ejection fraction to reduce the risk of cardiovascular death or hospitalization due to heart failure⁶
• EMPULSE, in adults hospitalized for acute heart failure and stabilized to improve clinical and patient reported outcomes⁷
• EMPACT-MI, to evaluate all-cause mortality and hospitalization for heart failure in adults with and without type 2 diabetes who have had an acute myocardial infarction, with the aim to prevent heart failure and improve outcomes⁸
• EMPA-KIDNEY, in adults with established chronic kidney disease to reduce the progression of kidney disease and the occurrence of cardiovascular death⁹
• EMPERIAL-Reduced, in adults with chronic heart failure with reduced ejection fraction to evaluate functional ability and patient reported outcomes¹⁰
• EMPERIAL-Preserved, in adults with chronic heart failure with preserved ejection fraction to evaluate functional ability and patient-reported outcomes¹¹
• EMPA-REG OUTCOME^®, in adults with type 2 diabetes and established cardiovascular disease to reduce the risk of major adverse cardiovascular events, including cardiovascular death³
• EMPRISE, two non-interventional studies (U.S. and EU-Asia) of the effectiveness, safety, healthcare utilization and cost of care of empagliflozin in routine clinical practice in adults with type 2 diabetes across the cardiovascular risk continuum^12,13

About Type 2 Diabetes and Cardiovascular Disease
Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.¹⁴ More than 463 million people worldwide have diabetes, of which 232 million are estimated to be undiagnosed.¹⁴ By 2045, the number of people with diabetes is expected to rise to 700 million people worldwide.14 Type 2 diabetes is the most common form of diabetes.¹⁴

Due to the complications associated with diabetes, such as high blood sugar, high blood pressure and obesity, cardiovascular disease is a major complication and the leading cause of death associated with diabetes.¹⁵ One in two people with type 2 diabetes worldwide die from a cardiovascular event.¹⁶

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.⁴

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.^17,18

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 Empagliflozin
Empagliflozin (marketed as Jardiance®) is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor and the first medicine approved by regulatory authorities to significantly reduce the risk of cardiovascular death or include data on the reduction of the risk of cardiovascular death in the label for adults with type 2 diabetes and established cardiovascular disease.^19,20,21

Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels prevents sugar being re-absorbed by the kidneys, leading to the excretion of excess sugar in the urine. In addition, initiation of empagliflozin also prevents salt being re-absorbed, leading to increased excretion of salt from the body and reducing the fluid load of the body’s blood vessel system (i.e. intravascular volume). Empagliflozin induces changes to the sugar, salt and water metabolism in the body that may contribute to the reductions in cardiovascular death observed in the EMPA-REG OUTCOME^® trial.²²

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 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.

Boehringer Ingelheim
Making new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.

As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of 19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.

We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.

More information about Boehringer Ingelheim can be found at www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.

About Lilly Diabetes
Lilly has been a global leader in diabetes care since 1923, when we introduced the world’s first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research, collaboration and quality manufacturing we strive to make life better for people affected by diabetes and related conditions. We work to deliver breakthrough outcomes through innovative solutions—from medicines and technologies to support programs and more. For the latest updates, visit http://www.lillydiabetes.com/ or follow us on Twitter: @LillyDiabetes and Facebook: LillyDiabetesUS.

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) and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug 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 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:
Stefanie Molkenthin
Product Communication Manager
Boehringer Ingelheim
Email: press@boehringer-ingelheim.com
Phone: +49 (6132) 77 172209

Stephan Thalen
Global Business Communications
Lilly Diabetes
Email: stephan.thalen@lilly.com
Phone: +1 (317) 276 8304

References

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