Initial results from the EMPRISE real-world study of empagliflozin compared with DPP-4 inhibitors presented at ACC.19 and AMCP 2019 

Ingelheim, Germany, and Indianapolis, US, 28 March 2019 – Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced initial results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) real-world evidence study that show that empagliflozin is associated with a 22 percent relative risk reduction in all-cause hospitalisations, compared to DPP-4 inhibitors, within a mean follow-up of 5.4 months.¹ Among those admitted to hospital, people treated with empagliflozin were discharged earlier compared to those treated with DPP-4 inhibitors (17,539 matched pairs in each treatment group).¹ 

Results also show that empagliflozin is associated with significantly fewer recurrent emergency department visits and physician’s office visits compared to DPP-4 inhibitors.¹ These initial results, observed during the first two years of the EMPRISE real-world evidence study evaluating US-only data, were presented at the Academy of Managed Care Pharmacy (AMCP) Annual Meeting 2019 in San Diego, US.

Initial EMPRISE results support data from the landmark EMPA-REG OUTCOME^® trial, which showed a relative risk reduction of 11 percent in all-cause hospitalisations with empagliflozin in people with type 2 diabetes and established cardiovascular disease.³

“People with diabetes are more likely to be admitted to hospital from any cause than those without the condition, experiencing longer and more costly hospital stays. This can have a substantial impact on healthcare resources,” said Dr Mehdi Najafzadeh, PhD, MSc, MA, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Instructor in Medicine, Harvard Medical School and study co-investigator. “Initial results from the EMPRISE real-world study show that empagliflozin is associated with a relative risk reduction in hospitalisations and with a shorter length of hospital stay for people with type 2 diabetes.” 

Initial effectiveness and safety data from EMPRISE were also recently presented at the American College of Cardiology’s 68th Annual Scientific Session & Expo in New Orleans, US (ACC.19). Results show that empagliflozin was associated with a 42 percent relative risk reduction in hospitalisation for heart failure* or all-cause mortality compared to DPP-4 inhibitors, and was not associated with a statistically significant increased risk of bone fracture or lower leg amputation compared to DPP-4 inhibitors.² These results support the findings from the EMPA-REG OUTCOME^® trial, which showed that empagliflozin reduced the relative risk of hospitalisation for heart failure or cardiovascular death in people with type 2 diabetes and established cardiovascular disease by 34 percent, with no imbalance with bone fractures or lower leg amputation.⁴  

About EMPRISE (NCT03363464, EUPAS20677)⁵
EMPRISE was initiated in 2016 to complement the EMPA-REG OUTCOME^® trial results and provide a comprehensive clinical picture of empagliflozin in routine care. By study completion, EMPRISE will provide insights into the comparative effectiveness, safety, healthcare resource utilisation and costs of empagliflozin, compared with DPP-4 inhibitors, in people with type 2 diabetes with and without cardiovascular disease in routine clinical care.
 
The study will assess the first five years of empagliflozin use in the US between 2014 and 2019. Over 200,000 people with type 2 diabetes from two commercial US healthcare providers and Medicare are projected to be included by study completion. From 2019, additional EMPRISE studies including analyses of data from 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)⁴ 
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 for blood pressure and cholesterol). 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 Diabetes and Cardiovascular Disease
More than 425 million people worldwide have diabetes, of which over 212 million are estimated to be undiagnosed.⁶ By 2045, the number of people with diabetes is expected to rise to 629 million people worldwide.⁶ Type 2 diabetes is the most common form of diabetes, responsible for around 90 percent of diabetes cases in high-income countries.⁶ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.⁶ 

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.^7,8 People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes.⁸ In 2017, diabetes caused four million deaths worldwide, with cardiovascular disease as the leading cause.⁶ Approximately 50 percent of deaths in people with type 2 diabetes worldwide are caused by cardiovascular disease.^9,10

Having a history of diabetes at age 60 can shorten a person’s life span by as much as six years compared with someone without diabetes. And having both diabetes and a history of heart attack or stroke by age 60 can shorten a person’s life span by as much as 12 years compared with someone without these conditions.¹¹

More than 60 guidelines have been updated to endorse type 2 diabetes agents with proven cardiovascular benefits since 2016, including a Consensus Report initiated by the American Diabetes Association^® and European Association for the Study of Diabetes, recommending that, in patients with type 2 diabetes and established atherosclerotic cardiovascular disease, SGLT2 inhibitors (such as empagliflozin) or GLP1 receptor agonists with proven cardiovascular benefits are recommended as part of glycaemic management.^12,13

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.^14,15,16

Inhibition of SGLT2 with empagliflozin in people with type 2 diabetes and high blood sugar levels leads to excretion of excess sugar in the urine. In addition, initiation of empagliflozin increases excretion of salt from the body and reduces 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.

About Boehringer Ingelheim and Eli Lilly and Company 
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centres on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world’s leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of people with diabetes and stand together to focus on patient needs. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributed to the alliance.

About Boehringer Ingelheim 
Improving the health and quality of life of patients 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 2017, Boehringer Ingelheim achieved net sales of nearly 18.1 billion euros. R&D expenditure, exceeding three billion euros, corresponded to 17.0 percent of net sales. 

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success, rather than short-term profit. 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: 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 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 healthcare leader that unites caring with discovery to 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 www.lilly.com and www.lilly.com/newsroom/social-channels.  

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 the expansion of clinical trials to evaluate empagliflozin as a treatment for adults with type 1 diabetes mellitus 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. 

CONTACT:

Dr Petra Kienle
Product Communication Manager
Boehringer Ingelheim 
Email: press@boehringer-ingelheim.com
Phone: +49 (6132) 77 143877

Stephan Thalen
Global Business Communications
Lilly Diabetes
Email: stephan.thalen@lilly.com
Phone: +1 317 903 5640