Phase III data show significant reduction in blood glucose with investigational compound empagliflozin added to metformin or metformin plus sulfonylurea in adults with type 2 diabetes

RIDGEFIELD, Conn. and INDIANAPOLIS, June 22, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results of two phase III 24-week clinical trials of the investigational agent empagliflozin^* added to metformin with and without the addition of sulfonylurea, in people with type 2 diabetes (T2D). The results showed statistically significant improvements in blood glucose as measured by reductions in HbA_1c (average blood glucose) after 24 weeks among people who received empagliflozin.^1,2

Empagliflozin is a member of the sodium glucose co-transporter-2 (SGLT2) inhibitor class of compounds, and is being investigated for the reduction of blood glucose levels in adults with T2D. The emerging SGLT2 inhibitor class removes excess glucose through the urine by blocking glucose re-absorption by the kidney.

The study, presented at the American Diabetes Association 73rd Scientific Sessions^®, also demonstrated statistically significant reductions in key secondary endpoints, including mean daily glucose concentration and body weight.^1,2 Overall, adverse events were reported in a similar percentage of patients treated with empagliflozin 10 mg, empagliflozin 25 mg and placebo.

"We are particularly encouraged by the blood sugar lowering results of this study with empagliflozin as an add-on to metformin or metformin plus sulfonylurea therapies," said Christophe Arbet-Engels, MD, PhD, vice president, metabolic-clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Metformin is commonly the first pharmacological treatment used to treat type 2 diabetes. However, because of the progressive nature of the disease, many patients are not meeting their blood sugar level goals and have difficulties managing other risk factors such as weight and increased blood pressure."

24-week Study with Empagliflozin as Add-on to Metformin
In this 24-week randomized, double-blind, placebo-controlled trial, the addition of empagliflozin to a background of metformin showed a placebo-adjusted reduction in HbA_1c of 0.57 percent and 0.64 percent (p<0.001) for empagliflozin 10 mg (n=217) and 25 mg (n=213), respectively, compared with placebo (n=207).¹ The study also showed a statistically significant placebo-adjusted reduction at 24 weeks in mean daily glucose concentration of 8 mg/dL with empagliflozin 10 mg (p=0.006) and 12 mg/dL with empagliflozin 25 mg (p<0.001).¹ Body weight also significantly decreased by 3.6 lbs and 4.4 lbs (p<0.001) with the addition of empagliflozin 10 mg and 25 mg, respectively, compared with metformin.

Drug-related adverse events were reported by 16.1 percent, 12.6 percent, and 12.1 percent of patients on empagliflozin 10 mg, empagliflozin 25 mg, and placebo, respectively. Confirmed hypoglycemia was reported in 1.8 percent of patients on empagliflozin 10 mg, 1.4 percent on empagliflozin 25 mg and 0.5 percent on placebo, none of which required assistance. Adverse events consistent with urinary tract infection were reported in 5.1 percent of patients on empagliflozin 10 mg, 5.6 percent on empagliflozin 25 mg and 4.9 percent on placebo. Adverse events consistent with genital infection were reported in 3.7 percent of patients on empagliflozin 10 mg, 4.7 percent on empagliflozin 25 mg and 0.0 percent on placebo.

24-week Study with Empagliflozin as Add-on to Metformin and Sulfonylurea
In this 24-week randomized, double-blind, placebo-controlled trial, the addition of empagliflozin to a background of metformin plus sulfonylurea therapy showed a placebo-adjusted reduction in HbA_1c of 0.64 percent and 0.59 percent (p<0.001) for empagliflozin 10 mg (n=225) and 25 mg (n=216), respectively, compared with placebo (n=225).² The study also showed statistically significant placebo-adjusted reductions at 24 weeks in mean daily glucose concentration of 10.02 mg/dL and 13.06 mg/dL (p<0.001) with empagliflozin 10 mg and 25 mg., respectively. Reductions in body weight were significantly greater with the addition of empagliflozin to metformin plus sulfonylurea (change in body weight of 3.88 lbs, 10 mg; and 4.39 lbs, 25mg; p<0.001).²

Drug-related adverse events were reported by 24.1 percent, 19.8 percent and 15.1 percent of patients on empagliflozin 10 mg, empagliflozin 25 mg, and placebo, respectively. Confirmed hypoglycemia was reported in 16.1 percent of patients on empagliflozin 10 mg, 11.5 percent on empagliflozin 25 mg and 8.4 percent on placebo, none of which required assistance. Adverse events consistent with urinary tract infection were reported in 10.3 percent of patients on empagliflozin 10 mg, 8.3 percent on empagliflozin 25 mg and 8.0 percent on placebo. Adverse events consistent with genital infection were reported in 2.7 percent of patients on empagliflozin 10 mg, 2.3 percent on empagliflozin 25 mg and 0.9 percent on placebo.

About the Empagliflozin Phase III Clinical Trial Program
Empagliflozin is being investigated in adults with T2D in a phase III clinical trial program that has enrolled more than 14,500 patients. This program includes more than 10 multinational clinical trials, including a large cardiovascular outcomes trial.

About Diabetes
Approximately 25.8 million Americans³ and an estimated 371 million people worldwide⁴ have type 1 or type 2 diabetes. T2D is the most common type, accounting for an estimated 90 to 95 percent of all diabetes cases.³ Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin.⁵ Diabetes was estimated to cost the U.S. $245 billion in direct medical costs and reduced productivity in 2012.⁶

Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in the field of diabetes that centers on three compounds representing several of the largest diabetes treatment classes. This alliance leverages the companies' strengths as two of the world's leading pharmaceutical companies, combining Boehringer Ingelheim's solid track record of research-driven innovation and Lilly's innovative research, experience, and pioneering history in diabetes. 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
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 140 affiliates and more than 46,000 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.

As a central element of its culture, Boehringer Ingelheim has a demonstrated commitment to corporate social responsibility. 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 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5 percent of its net sales. For more information please visit www.us.boehringer-ingelheim.com.

About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, IN, Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.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 work to meet the diverse needs of people with diabetes through research and collaboration, a broad and growing product portfolio and a continued commitment to providing real solutions – from medicines to support programs and more – to make lives better.

For more information, visit www.lillydiabetes.com.

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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 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.

CONTACT:

Catherine London
Associate Director, Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
Email: [email protected]
Phone: (203) 798-4638

Tammy Hull
Communications Manager
Lilly Diabetes
Email: [email protected]
Phone: (317) 651-9116

References

1. Haring H, et al. Empagliflozin as Add-On to Metformin for 24 Weeks Improves Glycemic Control in Patients with Type 2 diabetes (T2DM). Poster No: 1092-P. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions^®. June 21-25, Chicago, IL.
2. Haring H, et al. Empagliflozin as Add-On to Metformin Plus Sulfonylurea (SU) for 24 Weeks Improves Glycemic Control in Patients with Type 2 diabetes (T2DM). Poster No: 1082-P. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions^®. June 21-25, Chicago, IL.
3. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and pre-diabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, 2011.
4. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2012.
5. International Diabetes Federation. Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: June 18, 2013
6. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013; 36(4):1033-1046.

[*]Empagliflozin is an investigational compound. Its safety and efficacy have not been established.

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SOURCE Eli Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.