Phase III data show investigational compound empagliflozin reduced blood glucose in adults with Type 2 Diabetes treated with basal insulin

Ingelheim, Germany and Indianapolis, US, 22 June 2013 - Boehringer Ingelheim and Eli Lilly and Company today announced results of a 78-week Phase III clinical trial of the investigational compound empagliflozin* as an add-on to basal insulin in people with Type 2 Diabetes (T2D). The study, presented at the American Diabetes Association^® (ADA) 73rd Scientific Sessions, showed that empagliflozin 10mg and 25mg, produced statistically significant reductions in HbA1c (average blood glucose), compared to placebo as add-on to basal insulin, at the time of assessment of the study’s primary endpoint, week 18, as well as at week 78.¹

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.

"This study is an important component of the clinical programme of the Boehringer Ingelheim and Lilly Diabetes alliance, which is designed to examine empagliflozin as an add-on therapy to a broad range of existing treatments for people with Type 2 Diabetes," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The results observed in this study are encouraging as empagliflozin in combination with basal insulin demonstrated significant improvements in glucose control as well as weight loss".

The study included an 18-week fixed insulin dose period, after which the dose was adjusted at investigator discretion.¹ Results of the study with empagliflozin as an add-on to basal insulin in people with T2D included:

• At week 18, placebo-adjusted reductions in HbA1c for empagliflozin 10mg and 25mg of 0.6% and 0.7% (p<0.001), respectively.¹
• Confirmed hypoglycaemia (glucose ≤70mg/dL and/or requiring assistance) was reported in 20%, 28% and 21% of patients on empagliflozin 10mg, 25mg and placebo respectively, at week 18. 
• At week 78, placebo-adjusted reductions in HbA1c for empagliflozin 10mg and 25mg of 0.5% and 0.6% (p<0.001), respectively. Daily insulin dose was changed from baseline by -1.2IU, -0.5IU and 5.5IU for empagliflozin 10mg, 25mg and placebo, respectively.¹
• Both empagliflozin doses and placebo had comparable confirmed hypoglycaemic events (glucose ≤70mg/dL and/or requiring assistance); 36% reported by patients on both empagliflozin 10mg and 25mg, and 35% on placebo, at week 78.

Adverse events were reported by 85% and 87% of patients on empagliflozin 10mg and 25mg, respectively and by 87% of patients on placebo at week 78. Common adverse events included hypoglycaemia (see rates detailed above - 2 patients on empagliflozin 25mg required assistance), as well as adverse events consistent with urinary tract infection (reported in 15%, 12% and 9% of patients on empagliflozin 10mg, 25mg and placebo, respectively) and genital infection (reported in 8%, 5% and 2% of patients on empagliflozin 10mg, 25mg and placebo, respectively).

Further analysis also showed at week 78:

• A statistically significant reduction in body weight of 2.2kg (p<0.001) and 2.0kg (p<0.001) for empagliflozin 10mg and 25mg, respectively, compared to an increase of 0.7kg for placebo.¹
• Changes in systolic blood pressure were statistically significant in the empagliflozin 10mg group [-4.1mmHg (p=0.004)] but not in the empagliflozin 25mg group [-2.4mmHg (p=0.099)], compared to placebo [0.1mmHg].¹

About the study
The 78-week, randomised, double-blind placebo-controlled trial investigated the safety and efficacy of empagliflozin as an add-on to basal insulin in people with T2D. Patients were randomised to receive empagliflozin 10mg (n=169), empagliflozin 25mg (n=155) or placebo (n=170). Basal insulin dose remained constant for the first 18 weeks. Thereafter, adjustments were allowed at investigator discretion. Primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in insulin dose and HbA1c at week 78.¹

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.² Type 2 Diabetes is the most common type, accounting for an estimated 90–95% of all diabetes cases.³ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.⁴

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.