Type 2 diabetes: Investigational compound empagliflozin as an add-on therapy significantly reduced blood glucose and body weight in two newly presented phase III trials

RIDGEFIELD, Conn. and INDIANAPOLIS, June 16, 2014 – Two phase III clinical trials studying the efficacy and safety of the investigational compound empagliflozin in type 2 diabetes (T2D) were presented today at the American Diabetes Association 74th Scientific Sessions^®, Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Eli Lilly and Company (NYSE: LLY) announced. In a two-year study, empagliflozin demonstrated significantly greater decreases in hemoglobin A1C (a measure of average blood glucose over the past two to three months), body weight and blood pressure compared with glimepiride as add-on to metformin in adults with T2D. In a 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.

“Type 2 diabetes is a challenging disease to manage because blood sugar levels are often not adequately controlled with just one medication. We are encouraged by the findings that empagliflozin in combination with other therapies reduced blood glucose levels and body weight in adults with type 2 diabetes in both of these studies,” said Christophe Arbet-Engels, M.D., Ph.D., vice president, metabolic clinical development and medical affairs, BIPI. “These new data add to the known clinical profile for empagliflozin and bolster its large clinical registration program.”

Empagliflozin versus glimepiride as add-on to metformin for two years
A two-year study of 1,545 randomized and treated adults with T2D compared the efficacy and safety profiles of empagliflozin 25 mg with glimepiride (1-4 mg), each in combination with metformin. At 104 weeks, patients taking empagliflozin had significantly greater reductions in A1C, body weight and systolic and diastolic blood pressure from baseline compared with patients taking glimepiride:

• Mean reduction in A1C levels was 0.66 percent for empagliflozin compared with 0.55 percent for glimepiride.
• Mean change in body weight was a loss of 3.1 kg for empagliflozin compared with a gain 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 hypoglycemic events were reported for empagliflozin compared with glimepiride (2.5 percent vs. 24.2 percent, respectively). Overall adverse event rates in the two arms were 86.4 percent and 86.3 percent for empagliflozin and glimepiride, respectively. Urinary tract infections were reported in 13.7 percent of patients in the empagliflozin arm and 13.1 percent of patients in the glimepiride arm, and genital infections were reported in 11.8 percent and 2.2 percent for empagliflozin and glimepiride, respectively.

Empagliflozin versus placebo in obese, inadequately controlled patients with T2D on multiple daily insulin injections
In a 52-week, placebo-controlled study, the safety and efficacy of empagliflozin 10 mg or 25 mg added onto multiple daily insulin injections, with or without metformin, was studied in obese adults with T2D and inadequately controlled blood glucose levels. Mean baseline A1C level for patients in this study was 8.3 percent.

After 18 weeks, empagliflozin 10 mg and 25 mg significantly reduced A1C levels by 0.94 percent and 1.02 percent from baseline, respectively, compared with 0.50 percent with placebo. After 52 weeks, empagliflozin 10 mg and 25 mg significantly reduced A1C by 1.18 percent and 1.27 percent, respectively, compared with 0.81 percent with placebo, indicating further A1C reductions in both empagliflozin groups between 18 and 52 weeks.

After 52 weeks, patients in the empagliflozin 10 mg and 25 mg arms 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 arm were taking. More patients with baseline A1C greater than or equal to 7 percent treated with empagliflozin also achieved A1C levels below 7 percent (19.5 percent, 31 percent and 15.1 percent of patients in the empagliflozin 10 mg, 25 mg and placebo arms, respectively).

After 52 weeks, patients in each of the empagliflozin arms had an average body weight loss of 2 kg, compared with a gain of 0.4 kg for those in the placebo arm.

Hypoglycemia was reported in 51.1 percent, 57.7 percent and 58.0 percent of patients in the empagliflozin 10 mg, 25 mg and placebo arms, respectively.

About Empagliflozin
Empagliflozin is an investigational sodium glucose co-transporter-2 (SGLT2) inhibitor and is being studied for the reduction of blood glucose levels in adults with diabetes. The emerging SGLT2 inhibitor class removes excess glucose through the urine by blocking glucose re-absorption in the kidney. Empagliflozin is being studied in one of the largest clinical registration programs in its class, comprised of more than 10 multinational clinical trials and more than 13,000 adults with T2D.

About Diabetes
Approximately 24.4 million Americans and an estimated 382 million people worldwide have type 1 or type 2 diabetes. T2D is the most common type, accounting for an estimated 85 to 95 percent of all diabetes cases. Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.¹

Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers 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 Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.

For more information please visit http://www.us.boehringer-ingelheim.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.

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.

This press release contains forward-looking statements about empagliflozin, an investigational compound that is being studied for 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 receive regulatory approvals or 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.

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Tammy Hull
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Lilly Diabetes
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