Pooled analysis demonstrated reductions in systolic blood pressure with empagliflozin, an investigational SGLT-2 inhibitor, independent of changes in blood glucose and weight in adults with type 2 diabetes

RIDGEFIELD, Conn. and INDIANAPOLIS, Oct. 2, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announce data from a pooled analysis of two phase IIb trials in adults with type 2 diabetes (T2D) for an investigational SGLT-2 inhibitor, empagliflozin, at the 48^th European Association for the Study of Diabetes (EASD) Annual Meeting in Berlin. The new analysis showed a reduction in systolic blood pressure with empagliflozin, which, in the study, was independent of the reductions observed in blood glucose or weight, based on a statistical measure called the Pearson correlation coefficient.¹

Empagliflozin is part of a class of drugs being investigated for the reduction of blood glucose levels in adults with T2D. SGLT-2 inhibitors have been shown to reduce blood glucose, measured as hemoglobin A1c (HbA1c or A1C), by acting independently of insulin action. A1C is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months.

"Most classes of currently available oral T2D treatments depend on the actions of the hormone insulin to lower elevated blood glucose. The emerging SGLT-2 inhibitor class removes glucose through the urine by blocking glucose re-absorption in the kidney," said Christophe Arbet-Engels, MD, PhD, MBA, vice president, metabolic-clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Through the Boehringer Ingelheim and Lilly Diabetes Alliance, we are using our collective scientific expertise to address patient needs arising from the growing global diabetes epidemic. Together, we are committed to developing new medicines to address patients with this disease."

The pooled analysis includes data from two randomized, double-blind, placebo-controlled trials with treatment durations of 12 weeks (poster #770), assessing the safety and efficacy of empagliflozin alone (n=408) or as add-on to metformin (n=495) in adult patients with T2D. Patients were treated with either empagliflozin 10 mg or 25 mg.¹ At week 12, the investigators assessed changes in both systolic and diastolic blood pressure, as well as calculated the Pearson correlation coefficients to measure whether changes in A1C or weight were related to changes in systolic blood pressure (SBP). Researchers also analyzed a subgroup of patients with an SBP >140 mmHg at baseline.

At week 12, reductions in mean SBP of 3.8 mmHg and 4.5 mmHg were observed with empagliflozin 10 mg and 25 mg, respectively, versus 1.2 mmHg for placebo. Mean SBP at baseline of 131.3 mmHg and 132.5 mmHg were observed with empagliflozin 10 mg and 25 mg, respectively, versus 134.3 mmHg with placebo. For both dosages, this reduction in SBP was statistically significant compared to placebo. In patients with higher SBP at baseline (>140 mmHg), mean reductions of 17.0 mmHg and 13.4 mmHg were observed with empagliflozin 10 mg and 25 mg, respectively, and 10.4 mmHg with placebo.¹

Reductions in diastolic blood pressure (DBP) were numerically greater with both empagliflozin doses compared to placebo, but the differences did not reach statistical significance. For the entire cohort, the reductions in DBP were 2.3 mmHg and 2.7 mmHg for empagliflozin 10mg and 25mg, respectively, and 1.8 mmHg for placebo.¹ For patients with high DBP (>85 mmHg), reductions were 8.1 mmHg and 7.6 mmHg for empagliflozin 10mg and 25mg, respectively, and 6.1 mmHg for placebo.² 

Overall, changes in systolic and diastolic blood pressure did not correlate with changes in pulse rate or A1C.¹ The Pearson correlation coefficients between weight and SBP changes were 0.10 and 0.04 for empagliflozin 10 mg and 25 mg, respectively, and 0.12 for placebo. Between A1C and SBP changes, the coefficients were -0.09 and -0.02 for empagliflozin 10 mg and 25 mg, respectively, and 0.11 for placebo. None of these correlations reached statistical significance.¹

"As many as two of three adults with diabetes have high blood pressure, which can raise the risk of other health complications in this population," said Carol Wysham, MD, Clinical Associate Professor of Medicine at the University of Washington School of Medicine. "It is important that we continue researching potential treatments that may help patients with type 2 diabetes control their blood glucose levels."

Adverse events (AEs) at week 12 were experienced by 34.2% and 31.6% of patients who received empagliflozin 10 mg and 25 mg, respectively, and by 34.6% who received placebo.¹ The most commonly observed AEs included urinary tract and genital infections, generally categorized as mild, as seen in all clinical trials to date.²

Empagliflozin is being investigated in a phase III clinical trial program in adults with T2D with over 14,500 patients planned to be enrolled.² There are 12 ongoing multinational phase III clinical trials, including a large cardiovascular outcome trial. Empagliflozin pivotal studies could complete in late 2012, with filing planned in the U.S. and Europe in 2013.

About Diabetes
Approximately 25.8 million Americans³ and an estimated 366 million people worldwide⁴ have type 1 or type 2 diabetes. Type 2 diabetes is the most common type, accounting for an estimated 90 to 95 percent of all diabetes cases.³ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.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 four pipeline compounds representing several of the largest 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
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 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 pledges to act socially responsible. 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 2011, Boehringer Ingelheim achieved net sales of about $17.1 billion (13.2 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

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.

This press release contains forward-looking statements about empagliflozin, a compound under investigation. 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 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.

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1. Hach T, Lambers Heerspink HJ, Pfarr E, et al. The sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin lowers blood pressure independent of weight or HbA1c changes. [Abstract #770]. Presented at the 48th European Association for the Study of Diabetes (EASD) Annual Meeting. October 1-5, Berlin.
2. Data on file, Boehringer Ingelheim Pharmaceuticals, Inc.
3. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
4. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2011.
5. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: September 24, 2012.

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SOURCE Eli Lilly and Company; Boehringer Ingelheim