Analyses presented at EASD support Trajenta^® (linagliptin) as effective and well-tolerated for patients with type 2 diabetes with different background therapies

Berlin, Germany, 2nd October 2012 – Boehringer Ingelheim and Eli Lilly and Company today announced results from a large Phase III study and three pooled analyses of Phase III data presented at the 48th European Association for the Study of Diabetes (EASD) Annual Meeting, which support Trajenta^® (linagliptin) as effective and well-tolerated for patients with type 2 diabetes (T2D), including the elderly and those with diabetic nephropathy.^1,2,3,4 Linagliptin is a once-daily tablet that is used as monotherapy in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to intolerance, or contraindicated due to renal impairment. Linagliptin is also approved in combination with metformin and metformin + sulphonylurea.⁵

"Unfortunately type 2 diabetes can be a complex and challenging condition to treat," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “Many patients are elderly, or are affected by co-morbidities. As our clinical evidence base grows, so does our confidence that linagliptin offers an effective and well-tolerated treatment option for patients with type 2 diabetes in need of effective blood glucose control.”

Boehringer Ingelheim and Eli Lilly presented the results of a Phase III study, which evaluated the long-term safety and efficacy of the addition of linagliptin vs. placebo in 1261 patients inadequately controlled on basal insulin therapy*. The overall safety and tolerability for linagliptin was comparable to placebo. The incidence of hypoglycaemia was also comparable in both groups (linagliptin 31.4%, placebo 32.9%), despite better glycaemic control with linagliptin (-0.53% placebo-adjusted change in HbA1c from baseline at week 52 (P<0.0001). HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. Body weight was stable over the treatment period in both groups.¹

Linagliptin as add-on to basal insulin therapy* has also shown safety and efficacy in elderly patients (≥ 70 years) in a separate pre-specified pooled analysis of two Phase III studies, evaluating linagliptin vs. placebo as add-on therapy to basal insulin and as T2D management in elderly patients, over 24 weeks. Elderly patients with T2D are commonly characterised by longer disease duration and diminished beta-cell capacity, which often requires combination therapy with basal insulin. In this vulnerable elderly population, linagliptin in combination with basal insulin was well-tolerated with the overall incidence of adverse events (AE) not higher than placebo. Linagliptin achieved improvements in glycaemic control of -0.77% (placebo-adjusted change in HbA1c from baseline (P<0.0001)), without excessive risk of hypoglycaemia (hypoglycaemia occurred in 28.6% on linagliptin and 37.2% on placebo).⁴

A third analysis of seven Phase III trials assessed a variety of safety and efficacy parameters associated with linagliptin use in elderly T2D patients (≥ 65 years) as monotherapy or add-on to various glucose-lowering therapies. Results from this analysis showed that linagliptin is well-tolerated and might be a treatment option for elderly patients (≥ 65 years) without the need for dose adjustment.*

Linagliptin showed a reduction in glucose levels as measured by a −0.62% (P<0.0001, placebo-adjusted) change in HbA1c from baseline to week 24. Patients treated with linagliptin also experienced a significantly greater reduction in fasting plasma glucose (FPG) (placebo-adjusted mean change of −14.8 mg/dL, P<0.0001; −0.82 mmol/L) and the number of AEs was not higher than those on placebo (71.3% vs. 73.3%). Drug-related AEs were also not higher with linagliptin compared to placebo (18.1% vs. 19.8%).³

"This is very encouraging data in this often challenging-to-treat patient population," said Professor Anthony Barnett, Emeritus Professor of Medicine, University of Birmingham, UK. "Many elderly patients have additional safety and tolerability concerns, such as co-morbidities, compromised renal function and heightened risk of hypoglycaemia. Linagliptin appears to be an effective and well-tolerated treatment option for type 2 diabetes in the elderly without the need for dose adjustment or extra monitoring even if kidney function declines. In a situation where treatment choices are more and more limited, linagliptin is a welcome addition to our therapeutic armamentarium."

In a separate analysis, linagliptin showed efficacy in another vulnerable T2D patient population – those with diabetic nephropathy. Many patients with T2D have diabetic nephropathy shortly after diagnosis, and may go on to develop end stage kidney disease. Currently, there are only very limited oral treatment options available for T2D patients with renal disease. An analysis of seven randomised trials was performed and data after 24 weeks of treatment were generated to allow pooling and two sets were defined: Diabetic nephropathy in earlier stages of T2D: patients with persistent albuminuria (30<=UACR [Urine Albumin-to-creatine Ratio] <=3000 mg/g) and stable treatment with an ACEi [Angiotensin Converting Enzyme inhibitor] or ARB [Angiotensin II Receptor Blocker] (Set 1); Diabetic nephropathy in elderly patients (≥65 years), who fulfilled UACR criteria (Set 2). Patients from Set 1 were treated with or without oral glucose lowering background therapies and patients from Set 2 had various glucose lowering background therapies, including insulin therapy.

Patients in Set 1 experienced placebo-corrected changes in HbA1c and fasting plasma glucose of -0.71% and -1.4 mmol respectively (both P<0.0001). Linagliptin also significantly lowered UACR by 33% (P<0.05). In Set 2 Linagliptin significantly lowered adjusted UACR by 30% (P<0.05). The reduction of albuminuria was beyond what may be expected by the glucose-lowering effects of linagliptin in both Sets.²

Linagliptin (5 mg, once daily) is marketed in Europe as Trajenta (linagliptin) and in the U.S. as Tradjenta (linagliptin), as a once-daily tablet that is used along with diet and exercise to improve glycaemic control in adults with T2D. Linagliptin should not be used in patients with Type 1 Diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine). In Europe, Linagliptin is not approved for use in combination with insulin. With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment**.⁵

About Diabetes
An estimated 366 million people worldwide have diabetes.⁶ T2D is the most common type, accounting for an estimated 90% of all diabetes cases.⁷ Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.⁸

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 endeavours.

In 2011, Boehringer Ingelheim achieved net sales of about 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 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 programs and more - to make lives better.
For more information, visit www.lillydiabetes.com.

This press release contains forward-looking statements about linagliptin tablets 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 commercialisation. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that linagliptin 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.