Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) today announced results of a post-hoc analysis of the landmark EMPA-REG OUTCOME® trial that were presented at the 55th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain. Results suggest that the risk reduction in cardiovascular events, including cardiovascular death and hospitalisation for heart failure, seen with empagliflozin in the EMPA-REG OUTCOME® trial in adults with type 2 diabetes and established cardiovascular disease, were not affected by the number of controlled cardiovascular risk factors.

“Reducing cardiovascular risk in people with type 2 diabetes can be challenging, particularly in those with uncontrolled cardiovascular risk factors, such as blood sugar levels and blood pressure,” said Waheed Jamal, M.D., Corporate Vice President and Head of CardioMetabolic Medicine, Boehringer Ingelheim. “It is therefore encouraging to see these findings from the EMPA-REG OUTCOME® trial in which empagliflozin was shown to improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular disease, irrespective of whether cardiovascular risk factors were controlled.”

In this post-hoc analysis, the cardiovascular benefits of empagliflozin – including risk reduction for cardiovascular death and hospitalisation for heart failure – were investigated in subgroups of people with type 2 diabetes and established cardiovascular disease based on their cardiovascular risk factor goals. These cardiovascular risk factor goals were: blood sugar levels; cholesterol levels or statin use; blood pressure; presence of albumin in the urine; use of blood pressure medication; use of aspirin; and smoking status.1

In the EMPA-REG OUTCOME® trial, empagliflozin provided a 38 percent reduction in the risk of cardiovascular death (HR 0.62; 95% CI 0.49-0.77), a 35 percent reduction in the risk of hospitalisation for heart failure (HR 0.65; 95% CI 0.50-0.85) and a 14 percent reduction in the risk of 3P-MACE (HR 0.86; 95% CI 0.74-0.99), and this post-hoc analysis demonstrates that these cardiovascular benefits were not affected by the number of risk factor goals achieved.1

“Approximately half of all deaths in people with type 2 diabetes are caused by cardiovascular disease. Therefore, ensuring both patients and healthcare professionals understand the importance of cardioprotection remains an urgent priority,” said Sherry Martin, MD, Vice President, Global Medical Affairs, Lilly. “We are pleased to see that these results demonstrate that empagliflozin can help to address this unmet need by offering benefits to people with type 2 diabetes and cardiovascular disease across the spectrum of cardiovascular risk.”

Recent updates to more than 60 treatment guidelines worldwide now include findings from the EMPA-REG OUTCOME trial® as part of their endorsement of treatments with proven cardiovascular benefits for people with type 2 diabetes and established cardiovascular disease.2 Specifically, in the new 2019 ESC Guidelines on diabetes, pre-diabetes and cardiovascular disease – developed in collaboration with EASD – and an Expert Consensus Decision Pathway issued by the American College of Cardiology in 2018, empagliflozin is the recommended SGLT2 inhibitor for its proven benefit in reducing the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.3,4

About EMPA-REG OUTCOME® (NCT01131676)5
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.5 Type 2 diabetes is the most common form of diabetes, responsible for around 90 percent of diabetes cases in high-income countries.Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin. 5

Due to 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. 7 In 2017, diabetes caused four million deaths worldwide, with cardiovascular disease as the leading cause.5 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

Worldwide, 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.2,12

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.13,14,15

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.