Recruitment complete for Trajenta^® (linagliptin) cardiovascular outcome study in patients with Type 2 Diabetes

Ingelheim, Germany, 08 November, 2012 – Boehringer Ingelheim and Eli Lilly and Company are pleased to announce that the recruitment of patients for CAROLINA (Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes)¹ has been completed. Linagliptin is currently the only DPP-4 inhibitor that is being compared to an active comparator in a long-term prospective cardiovascular (CV) outcome study.

“The impact of diabetes treatment options on CV complications is not well understood. This poor understanding poses a challenge for treating physicians given the high level of cardiovascular co-morbidity in Type 2 Diabetes patients,” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “CAROLINA will close the scientific gap in our understanding of long-term cardiovascular outcomes with linagliptin and glimepiride. This study illustrates our commitment to provide a strong scientific foundation for the best treatment options.”

The study includes over 6,000 patients in 43 countries at more than 670 sites across the globe. The aim of the study is to investigate and compare the long term impact of treatment with linagliptin and glimepiride on CV morbidity and mortality over a period of about 6–7 years.¹ In addition, the study will compare secondary measures of efficacy with regard to lowering blood glucose as well as safety parameters, including body weight and the incidence of hypoglycaemia.¹ A prior study compared linagliptin with glimepiride with the primary objective to evaluate the respective glucose-lowering efficacy of both compounds after two years of treatment. The study demonstrated similar glucose-lowering with both treatments, but linagliptin was associated with less hypoglycaemia and less weight gain compared to glimepiride. However, this prior study was not designed to thoroughly assess CV effects of both treatments.²

The primary endpoint of CAROLINA will be time to the first occurrence of either: CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for unstable angina pectoris.¹ The study is expected to complete in 2018.

The US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory authorities worldwide approved linagliptin for the treatment of adult patients with Type 2 Diabetes as monotherapy or in combination with metformin, as add-on therapy to insulin, with sulphonylurea and with pioglitazone and with metformin plus sulphonylurea (these last two combinations have only been approved by the FDA in the United States).^3,4 With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment*.³

About CAROLINA Study Design¹
CAROLINA evaluates the CV safety of linagliptin in comparison to glimepiride in patients with Type 2 Diabetes and at increased CV risk.
Inclusion criteria include at least one of the following:

• Previous vascular complications
• Evidence of end organ damage such as albuminuria
• Age >70 years
• Two or more specified traditional CV risk factors

Patients are predominantly on metformin background therapy, but the protocol also allows for patients with contraindications to metformin, e.g., due to renal impairment. Linagliptin 5 mg is being compared to glimepiride 1–4 mg in 6,000 patients with a 6–7 year follow-up.

About Linagliptin
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 Type 2 Diabetes. 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). With linagliptin, no dose adjustment is required regardless of declining renal function or hepatic impairment.³

About Diabetes
An estimated 366 million people worldwide have Type 1 and Type 2 Diabetes.⁵ Type 2 Diabetes is the most common type, accounting for an estimated 90% of all diabetes cases.⁶ Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin.⁷

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.