Type 2 Diabetes: Jardiance^® (empagliflozin) as an add-on therapy significantly reduced blood glucose and body weight in two newly presented Phase III trials

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Ingelheim, Germany and Indianapolis, US, 16 June, 2014 - Boehringer Ingelheim and Eli Lilly and Company presented results of two Phase III clinical trials studying the efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in adults with Type 2 Diabetes (T2D) at the American Diabetes Association 74th Scientific Sessions^®. Results showed that empagliflozin in combination with certain other diabetes therapies reduced blood glucose, body weight and blood pressure.

In a two-year study, empagliflozin demonstrated significantly greater reductions in blood glucose, body weight and blood pressure compared with glimepiride, when both were added-on to metformin in adults with T2D.¹ In a second, 52-week study of obese adults with T2D on high insulin doses with or without metformin, adding empagliflozin to multiple daily insulin injections significantly reduced blood glucose and body weight with lower insulin doses compared with placebo.²

"The progressive nature of Type 2 Diabetes often means that more than one medication is needed to manage blood glucose levels," said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. "The encouraging results from these trials show that empagliflozin taken in combination with either metformin, or with multiple daily injections of insulin, reduced blood glucose levels and body weight in adults with Type 2 Diabetes."

Empagliflozin versus glimepiride as add-on to metformin¹ This two-year study of 1,545 adults with T2D compared the efficacy and safety profiles of empagliflozin 25 mg with glimepiride (1–4 mg), each in combination with metformin. After two years, patients taking empagliflozin had significantly greater reductions in HbA1c (average blood glucose over the past two to three months), body weight and blood pressure compared with patients taking glimepiride:

• Mean reduction in HbA1c levels was 0.66 percent for empagliflozin compared with 0.55 percent for glimepiride.
• Mean change in body weight was a reduction of 3.1 kg for empagliflozin compared with an increase of 1.3 kg for glimepiride.
• Mean change in systolic blood pressure was a reduction of 3.1 mmHg for empagliflozin compared with an increase of 2.5 mmHg for glimepiride.
• Mean change in diastolic blood pressure was a reduction of 1.8 mmHg for empagliflozin compared with an increase of 0.9 mmHg for glimepiride.

Significantly fewer confirmed hypoglycaemic events were reported for empagliflozin compared with glimepiride (2.5 percent vs. 24.2 percent, respectively). Overall adverse event rates were similar in the two groups (86.4 percent and 86.3 percent, for empagliflozin and glimepiride, respectively). Urinary tract infections were reported in 13.7 percent of patients treated with empagliflozin and 13.1 percent of patients treated with glimepiride, and genital infections were reported in 11.8 percent and 2.2 percent, respectively.

Empagliflozin versus placebo in obese, inadequately controlled patients with T2D on multiple daily insulin injections²
This one year study of 375 obese adults with T2D and inadequately controlled blood glucose levels, assessed the safety and efficacy of empagliflozin 10 mg or 25 mg added on to multiple daily insulin injections, with or without metformin. Mean initial levels of HbA1c for patients in this study was 8.3 percent. Compared with placebo, patients in each of the empagliflozin groups had significant reductions in HbA1c at week 18 and 52. Results at week 52 also showed reductions in body weight and lower insulin doses with empagliflozin added to multiple daily insulin injections, versus placebo.

After 18 weeks:

• Significant reductions from initial HbA1c levels of 0.94 percent and 1.02 percent with empagliflozin 10 mg and 25 mg, respectively, compared to 0.50 percent with placebo.

After 52 weeks:

• Significant reductions from initial HbA1c levels of 1.18 percent and 1.27 percent with empagliflozin 10 mg and 25 mg, respectively, compared to 0.81 percent with placebo.
• Patients in the empagliflozin 10 mg and 25 mg groups were taking mean total daily insulin doses that were 8.8 IU/day and 11.2 IU/day lower, respectively, than the dose patients in the placebo group were taking.
• More patients with initial HbA1c levels greater than or equal to 7 percent and treated with empagliflozin, achieved HbA1c levels below 7 percent (31 percent, 42 percent and 21 percent of patients in the empagliflozin 10 mg, 25 mg and placebo groups, respectively).
• Average reduction in body weight of 2 kg for patients in each of the empagliflozin groups compared with a gain of 0.4 kg for those in the placebo group.

Hypoglycaemia was reported in 51.1 percent, 57.7 percent and 58.8 percent of patients in the empagliflozin 10 mg, 25 mg and placebo groups, respectively.

About Empagliflozin
Empagliflozin, marketed in Europe as Jardiance^® is an oral, once daily tablet for the treatment of adults with Type 2 Diabetes and is part of the SGLT2 inhibitor class. SGLT2 are proteins fundamental to the kidney’s role in filtering blood sugar and are responsible for about 90 percent of the reabsorption of glucose back into the bloodstream.³ In people with T2D, there is an overexpression of SGLT2, contributing to elevated blood glucose levels.⁴ Empagliflozin reduces the kidneys' ability to reabsorb glucose into the bloodstream, leading to urinary glucose excretion. Unlike most classes of existing oral T2D treatments, SGLT2 inhibitors like empagliflozin work independently of β-cell function and insulin pathway.

Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company entered into 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 patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

In 2013, Boehringer Ingelheim achieved net sales of about €14.1 billion. R&D expenditure corresponds to 19.5% of its net sales.

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 broad and growing product portfolio and a continued determination to provide real solutions—from medicines to support programs 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 http://newsroom.lilly.com/social-channels.

This press release contains forward-looking statements about empagliflozin for the treatment of type 2 diabetes. It reflects Lilly's current beliefs; however, as with any such undertaking, there are substantial risks and uncertainties in the process of drug development and commercialization. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that empagliflozin will prove to be commercially successful. For further discussion of these and other risks and uncertainties, please see Lilly's latest Forms 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.