Phase III data show significant reduction in blood glucose with investigational compound empagliflozin added to metformin or metformin plus sulphonylurea in adults with Type 2 Diabetes

Ingelheim, Germany and Indianapolis, US, 22 June 2013 - Boehringer Ingelheim and Eli Lilly and Company today announced results of two Phase III 24-week clinical trials of the investigational compound empagliflozin* added to metformin with and without the addition of sulphonylurea, respectively, in people with Type 2 Diabetes (T2D). These results showed statistically significant reductions in blood glucose among people who received empagliflozin, as measured by reductions in HbA1c (average blood glucose) after 24 weeks.^1,2

Empagliflozin is a member of the sodium glucose cotransporter 2 (SGLT2) inhibitor class of drugs 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 reducing glucose reabsorption in the kidney.

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

“Metformin is the foundation of treatment for Type 2 Diabetes in people without clinically relevant renal impairment. However, many people don’t meet their blood sugar target due to the progressive nature of the condition and have difficulties managing other risk factors such as weight and increased blood pressure,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “The results from this study of empagliflozin as an add-on to metformin or metformin plus sulphonylurea therapies are promising for people with Type 2 Diabetes”.

24-week study with empagliflozin as an add-on to metformin
In this 24-week randomised, double-blind, placebo-controlled trial, the addition of empagliflozin to a background of metformin showed a placebo-adjusted reduction in HbA1c of 0.57% (p<0.001) and 0.64% (p<0.001) for empagliflozin 10mg (n=217) and 25mg (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 of 8mg/dL (p=0.006) with empagliflozin 10mg and 12mg/dL (p<0.001) with empagliflozin 25mg.¹ Empagliflozin 10mg and 25mg also had a significant placebo-adjusted reduction in body weight of 1.63kg (p<0.001) and 2.01kg (p<0.001), respectively.¹

Further analysis also showed reductions in systolic blood pressure by 4.5mmHg (p<0.001) with empagliflozin 10mg and 5.2mmHg (p<0.001) with empagliflozin 25mg versus placebo.¹ Other analysis findings showed reductions in fasting plasma glucose by 20.04mg/dL (p<0.001) with empagliflozin 10mg and 22.28mg/dL (p<0.001) with empagliflozin 25mg versus placebo.¹

Adverse events were reported by 57.1% and 49.5% of patients on empagliflozin 10mg and 25mg, respectively, and 58.7% of patients on placebo. Common adverse events included hypoglycaemia (plasma glucose =70mg/dL and/or requiring assistance – reported in 1.8% of patients on empagliflozin 10mg, 1.4% on empagliflozin 25mg and 0.5% on placebo, none required assistance), as well as adverse events consistent with urinary tract infection (reported in 5.1% of patients on empagliflozin 10mg, 5.6% on empagliflozin 25mg and 4.9% on placebo) and genital infection (reported in 3.7% of patients on empagliflozin 10mg, 4.7% on empagliflozin 25mg and none on placebo).

24-week study with empagliflozin as an add-on to metformin and sulphonylurea
In this 24-week randomised, double-blind, placebo-controlled trial, the addition of empagliflozin to a background of metformin plus sulphonylurea therapy showed a placebo-adjusted reduction in HbA1c of 0.64% (p<0.001) and 0.59% (p<0.001) for empagliflozin 10mg (n=225) and 25mg (n=216), respectively, compared with placebo (n=225).2 The study also showed a statistically significant placebo-adjusted reduction at 24 weeks in mean daily glucose of 10.02mg/dL (p<0.001) and 13.06mg/dL (p<0.001) with empagliflozin 10mg and 25mg, respectively. Loss of weight greater than 5% was achieved by 27.6% and 23.6% of patients treated with empagliflozin 10mg and 25mg (p<0.001; 1.75kg and 1.99kg), respectively, as add-on to metformin plus sulphonylurea, versus 5.8% on placebo.²

Adverse events were reported by 67.9%, 64.1% and 62.7% of patients on empagliflozin 10mg, 25mg and placebo, respectively. Common adverse events include hypoglycaemia (plasma glucose =70mg/dL and/or requiring assistance – reported in 16.1% of patients on empagliflozin 10mg, 11.5% on empagliflozin 25mg and 8.4% on placebo; none required assistance), as well as adverse events consistent with urinary tract infection (reported in 10.3% of patients on empagliflozin 10mg, 8.3% on empagliflozin 25mg and 8.0% on placebo) and genital infection (reported in 2.7% of patients on empagliflozin 10mg, 2.3% on empagliflozin 25mg and 0.9% on placebo).

About the empagliflozin Phase III clinical trial programme
Empagliflozin is being investigated in adults with T2D in a Phase III clinical trial programme that plans to enrol more than 14,500 patients. This programme comprises more than 10 multinational clinical trials, including a large cardiovascular outcomes trial.

About diabetes
An estimated 371 million people worldwide have Type 1 or Type 2 Diabetes.³ Type 2 Diabetes is the most common type, accounting for an estimated 90–95% of all diabetes cases.⁴ Diabetes is a chronic condition 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 centres 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
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.

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 endeavours.

In 2012, Boehringer Ingelheim achieved net sales of about €14.7 billion. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

For more information please visit www.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 organisations. 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 programmes and more – to make lives better.

For more information, visit www.lillydiabetes.com.

This press release contains forward-looking statements about empagliflozin, a potential future treatment 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 commercialisation. 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.