Phase III study finds investigational agent empagliflozin significantly reduced blood glucose in adults with type 2 diabetes and impaired kidney function

RIDGEFIELD, Conn. and INDIANAPOLIS, June 22, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results of a 52-week phase III clinical trial of the investigational agent empagliflozin*, which showed statistically significant reductions in HbA_1c (average blood glucose) at week 24 with the addition of empagliflozin to existing oral antihyperglycemic therapy in adults with type 2 diabetes (T2D) and mild to moderate kidney impairment (eGFR>/=60 to <90 ml/min/1.73 m² and eGFR>/=30 to <60 ml/min/1.73 m²).¹

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.

Results from the study, presented at the American Diabetes Association 73rd Scientific Sessions^®, also demonstrated a significant reduction in body weight and blood pressure with empagliflozin versus placebo in patients with mild to moderate kidney impairment.¹ Adverse events (AEs) were reported in 79.6 percent, 75.4 percent and 72.7 percent of patients at 24 weeks with empagliflozin 10 mg, empagliflozin 25 mg and placebo, respectively.

"We are encouraged by the data from this phase III study," said Christophe Arbet-Engels, MD, PhD, vice president, metabolic-clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Many people with type 2 diabetes also are impacted by renal impairment. Through the Boehringer Ingelheim and Lilly Diabetes alliance, we are using our collective knowledge to find new treatment options for type 2 diabetes."

Results of the study with empagliflozin in patients with renal impairment included:

• Reductions in HbA_1c for empagliflozin of 0.52 percent and 0.68 percent (p<0.001) for 10 mg and 25 mg, respectively, at week 24 versus placebo in patients with mild renal impairment; for empagliflozin 25 mg, reduction in HbA_1c was 0.42 percent (p<0.001) in patients with moderate renal impairment versus placebo¹

Additionally, results of the study with empagliflozin in patients with renal impairment included the following exploratory endpoints:

• Decrease in fasting blood glucose (FPG) levels in patients with mild renal impairment of 13.88 mg/dL and 18.08 mg/dL (p<0.001) for empagliflozin 10 mg and 25 mg, respectively, and an increase of 5.67 mg/dL for placebo; in patients with moderate renal impairment, a decrease in FPG levels of 9.26 mg/dL (p<0.001) for empagliflozin 25 mg and an increase of 10.16 mg/dL for placebo¹
• Loss of 3.88 lbs and 5.14 lbs in body weight for empagliflozin 10 mg and 25 mg, respectively (p<0.001) compared with 0.73 lbs for placebo in patients with mild renal impairment; loss of 2.16 lbs in body weight for empagliflozin 25 mg (p<0.001) compared with 0.176 lbs for placebo in patients with moderate renal impairment¹
• Improvements in systolic blood pressure (SBP) with empagliflozin versus placebo:
  • In patients with mild renal impairment, SBP decreased by 2.9 mmHg (p=0.033) and
    4.5 mmHg (p=0.002) for empagliflozin 10 mg and 25 mg, respectively, while it increased by 0.7 mmHg for placebo
  • In patients with moderate renal impairment, SBP decreased by 3.9 mmHg (p=0.001) for empagliflozin 25 mg and increased by 0.4 mmHg for placebo¹
• Improvements in diastolic blood pressure (DBP) with empagliflozin versus placebo:
  • In patients with mild renal impairment, DBP decreased by 1.4 mmHg (p=0.006) and
    2.2 mmHg (p<0.001) for empagliflozin 10 mg and 25 mg, respectively, while it increased by 1.1 mmHg for placebo
  • In patients with moderate renal impairment, DBP decreased by 1.7 mmHg (p=0.020) for empagliflozin 25 mg and increased by 0.2 mmHg for placebo.¹

The percentage of people with mild renal impairment who reported drug-related AEs at 52 weeks were 37.8 percent, empagliflozin 10 mg; 41.2 percent, empagliflozin 25 mg; and 32.6 percent, placebo. Drug-related AEs at 52 weeks in patients with moderate renal impairment were reported by 27.3 percent, empagliflozin 25 mg; and 24.1 percent, placebo. Observed AEs included hypoglycemia, events consistent with urinary tract infection, events consistent with genital infection, events consistent with volume depletion, and events consistent with bone fracture.

About the study
The 52-week randomized, double-blind, placebo-controlled trial investigated the safety and efficacy of empagliflozin as add-on to existing therapy in people with type 2 diabetes mellitus and renal impairment.¹ Patients with mild renal impairment received empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Patients with moderate or severe renal impairment received empagliflozin 25 mg or placebo. The primary endpoint was change from baseline in HbA_1c at week 24. Exploratory endpoints included changes from baseline in FPG, weight and BP at week 24.¹

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 people. In total, this program comprises more than 10 multinational clinical trials, including a large cardiovascular outcome trial.

About Diabetes
Approximately 25.8 million Americans² and an estimated 371 million people worldwide³ 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.² Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin⁴. Diabetes was estimated to cost the U.S. $245 billion in direct medical costs and reduced productivity in 2012.⁵

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 people 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: usnews@boehringer-ingelheim.com
Phone: (203) 798-4638

Tammy Hull
Communications Manager
Lilly Diabetes
Email: hullta@lilly.com
Phone: (317) 651-9116

References

*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.