Interim analysis from EMPRISE real-world study shows empagliflozin decreased risk of hospitalisation for heart failure compared with DPP-4 inhibitors and GLP-1 receptor agonists

Ingelheim, Germany, and Indianapolis, US, 17 November 2019 – A new interim analysis of three-year data from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) real-world study on effectiveness shows that empagliflozin was associated with a decreased risk of hospitalisation for heart failure and a similar risk of non-fatal atherosclerotic cardiovascular events compared with DPP-4 inhibitors and GLP-1 receptor agonists.¹ The interim analysis included 190,000 adults in the US with type 2 diabetes with and without cardiovascular disease. The results were shared today on behalf of Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) at the American Heart Association® Scientific Sessions 2019 in Philadelphia, US.

“Heart failure is the most common cause of hospitalisation among individuals aged 65 years and over in Europe and the US. It is therefore encouraging to see that, in addition to the clinical trial setting, empagliflozin has been seen to reduce the risk of heart failure hospitalisation in people with type 2 diabetes in routine clinical practice,” said Waheed Jamal, MD, Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “On top of this, as one in three people with type 2 diabetes has cardiovascular disease, it is encouraging to see similar results on risk of non-fatal atherosclerotic cardiovascular events with empagliflozin and other type 2 diabetes medications that have also previously shown favourable results for this endpoint.”

In this new interim analysis, empagliflozin was associated with a reduction in risk of hospitalisation for heart failure of 41 percent compared with DPP-4 inhibitors and of 17 percent compared with GLP-1 receptor agonists.¹ Risk for non-fatal atherosclerotic cardiovascular events – defined as non-fatal heart attack or stroke, hospitalisation for unstable angina or coronary revascularisation – was similar for those treated with empagliflozin (14.6 events per 1,000 patient-years) compared with DPP-4 inhibitors (17.6 events per 1,000 patient-years). The risk was also similar for those treated with empagliflozin (14.2 events per 1,000 patient-years) compared with GLP-1 receptor agonists (14.8 events per 1,000 patient-years).¹

In a second interim analysis of EMPRISE, which included more than 45,000 patients, empagliflozin was associated with a significant reduction in all-cause hospitalisations, emergency department visits and physician’s office visits compared with DPP-4 inhibitors.²

Results from the EMPRISE real-world study in routine clinical care complement data from the landmark EMPA-REG OUTCOME^® trial, in which empagliflozin showed a 35 percent relative risk reduction in hospitalisation for heart failure compared with placebo in adults with type 2 diabetes and established cardiovascular disease. The EMPA-REG OUTCOME^® trial also showed a 38 percent relative risk reduction in cardiovascular death in those taking empagliflozin versus placebo in the same population.³

“We are pleased to see the three-year data for EMPRISE continues to complement findings from the EMPA-REG OUTCOME trial,” said Sherry Martin, MD, Vice President, Global Medical Affairs, Lilly. “These new real-world findings are just one part of a broad and comprehensive clinical development programme, including a large heart failure programme, that explores how empagliflozin can improve patient health outcomes and potentially fill treatment gaps for people with cardiorenal metabolic conditions.” 

The effects of empagliflozin on heart failure-related outcomes and functional capacity in people with heart failure are being evaluated in the empagliflozin heart failure programme. The programme, which includes more than 9,500 adults with heart failure, including those with and without diabetes, consists of the EMPEROR-Reduced, EMPEROR-Preserved, EMPERIAL-Reduced, EMPERIAL-Preserved, EMPULSE and EMPA-VISION studies.^4,5,6,7,8,9

About EMPRISE^1,10,11
EMPRISE was initiated in 2016 to complement the EMPA-REG OUTCOME^® trial results by providing data on the comparative effectiveness, safety, healthcare resource utilisation and costs in routine clinical care compared with DPP-4 inhibitors in people with type 2 diabetes with and without cardiovascular disease. In addition, a sub-group analysis has provided data on the effectiveness of empagliflozin compared with GLP-1 receptor agonists.

The study will assess the first five years of empagliflozin use in the US between 2014 and 2019. Data analyses includes planned interim analyses (based on 12-month data updates) and a final analysis. More than 200,000 people with type 2 diabetes are projected to participate in the EMPRISE trial by its completion. From 2019, additional EMPRISE studies, including Asia and Europe, will provide insights from different regions of the world with an international perspective on the use of empagliflozin in routine clinical care. 

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

About EMPA-REG OUTCOME^® (NCT01131676)³
EMPA-REG OUTCOME^® was a long-term, multicentre, randomised, 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 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.¹² It is a widespread condition, affecting 60 million people worldwide, and expected to increase as the population ages.¹³ Heart failure is highly prevalent in people with diabetes; however, approximately half of all people with heart failure do not have diabetes.^14,15

Symptoms of heart failure include difficulty with breathing, swelling – most commonly in feet, legs and ankles – and fatigue, among others.¹⁶ People with heart failure experience a substantial reduction in quality of life, approximately 76 percent of whom find it difficult to carry out usual activities.¹⁷ This is, in part, due to limitation of physical activity.

There is a high unmet need in the treatment of heart failure, as approximately 50 percent of people diagnosed with heart failure will die within five years.¹⁸ Additionally, heart failure represents the most common cause of hospitalisation among individuals aged 65 years and over in the US and Europe.¹⁴

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 the label in several countries.^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 to help those living with heart failure or chronic kidney disease. 

Currently, no Boehringer Ingelheim and Lilly products are approved for the treatment of heart failure or chronic kidney disease. 

Boehringer Ingelheim 
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention. 

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas: human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 percent of net sales. 

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment. 

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: https://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 and collaboration, a wide range of therapies and a continued determination to provide real solutions – from medicines to support programmes and more – we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.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 chronic kidney disease and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialisation. 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. 
 
CONTACT:
Stefanie Dölz
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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² Najafzadeh M, Pawar A, Schneeweiss S, et al. Healthcare resource utilization among empagliflozin initiators with and without cardiovascular disease versus DPP4i in a commercially-insured routine care population: an analysis from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study. Presented at AHA Scientific Sessions 2019. 18 November 2019, Philadelphia, US. 
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⁷ A phase III randomised, double-blind trial to evaluate the effect of 12 weeks treatment of once daily EMPagliflozin 10 mg compared with placebo on ExeRcise ability and heart failure symptoms, In patients with chronic HeArt FaiLure with preserved Ejection Fraction (HFpEF) (EMPERIAL – preserved). Available at: https://clinicaltrials.gov/ct2/show/NCT03448406?term=EMPERIAL&rank=1. Accessed November 2019.
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