News Release

RIDGEFIELD, Conn. and INDIANAPOLIS, Nov. 8, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced the clinical trial enrollment of patients for CAROLINA (Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes) has been completed. Linagliptin is currently the only DPP-4 inhibitor that is being compared to a sulfonylurea in a long-term cardiovascular (CV) outcome study.

Linagliptin, marketed in the U.S. as Tradjenta®, is a once-daily tablet used along with diet and exercise to improve glycemic control in adults with type 2 diabetes. TRADJENTA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (increased ketones in the blood or urine).

The study includes over 6,000 patients in 43 countries at more than 600 sites around the world. The aim of the study is to investigate and compare the long-term impact on CV morbidity and mortality of treatment with TRADJENTA or glimepiride over a period of about 6—7 years.(1) Additionally, 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 hypoglycemia in patients with type 2 diabetes at elevated cardiovascular risk receiving usual care, and compare the outcome against glimepiride.(1) 

"CAROLINA will evaluate the cardiovascular safety of linagliptin compared to the sulfonylurea glimepiride," said Dr. Julio Rosenstock, Director of the Dallas Diabetes and Endocrine Center at Medical City in Dallas and Principal Investigator of the study. "Sulfonylureas are frequently used add-on therapy to metformin, which is considered the standard first-line therapy. This is the first time a DPP-4 inhibitor is being directly compared to a sulfonylurea in a long-term cardiovascular outcome study."

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

"There are limited available data reporting on CV-related comorbidities with current therapies for patients with type 2 diabetes. For the first time, this study has the potential to compare the CV morbidity, mortality and safety of the DPP-4 inhibitor linagliptin to the commonly prescribed sulfonylurea glimepiride," said Christophe Arbet-Engels, MD, PhD, MBA, vice president, metabolic-clinical development and medical affairs, Boehringer Ingelheim. "It is our hope CAROLINA will help us to better understand the effect on cardiovascular outcomes of linagliptin compared to glimepiride, and, therefore, add to the knowledge base  physicians use to decide how to treat their patients."

To learn more about TRADJENTA and for full prescribing information visit: www.TRADJENTA.com, or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257.

About CAROLINA Study Design(1)

CAROLINA evaluates the CV safety of linagliptin in comparison to glimepiride in patients with T2D and at increased CV risk.

Inclusion criteria include at least one of the following:

• Previous vascular disease
• Evidence of vascular-related end-organ damage such as albuminuria or retinopathy
• Age greater than or equal to 70 years
• Two or more specified traditional CV risk factors, such as hypertension or dyslipidemia

Patients are predominantly on metformin background therapy, but the protocol also allows patients with contraindications to metformin, e.g., due to renal impairment, to participate. Linagliptin 5 mg is being compared to glimepiride 1—4 mg, both as monotherapy or as add-on therapy to metformin or alpha-glucosidase inhibitors in at least 6,000 patients with a 6—7 year follow-up.

What are TRADJENTA (linagliptin) tablets?

TRADJENTA is a prescription medicine that is used along with diet and exercise to lower blood sugar in adults with type 2 diabetes.

TRADJENTA is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

Important Safety Information

Who should not take TRADJENTA?

Do not take TRADJENTA if you are allergic to linagliptin or any of the ingredients in TRADJENTA.

Symptoms of a serious allergic reaction to TRADJENTA are rash, raised red patches on your skin (hives), swelling of your face, lips, and throat that may cause difficulty breathing or swallowing. If you have any symptoms of a serious allergic reaction, stop taking TRADJENTA and call your doctor right away.

What should I tell my doctor before taking TRADJENTA?

Tell your doctor if you take other medicines that can lower your blood sugar, such as a sulfonylurea or insulin.

TRADJENTA may cause serious side effects, including low blood sugar (hypoglycemia). If you take TRADJENTA with another medicine that can cause low blood sugar, such as sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea or insulin may need to be lowered while you take TRADJENTA.

Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, or feeling jittery.

Also tell your doctor if you take rifampin (Rifadin®, Rimactane®, Rifater®, Rifamate®), an antibiotic that is used to treat tuberculosis.

TRADJENTA may affect the way other medicines work, and other medicines may affect how TRADJENTA works.

Tell your doctor if you are pregnant or planning to become pregnant or are breastfeeding or plan to breastfeed.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

What are the possible side effects of TRADJENTA?

The most common side effects of TRADJENTA include stuffy or runny nose and sore throat.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more safety information, please see Patient Information and full Prescribing Information.

TJ CONS ISI August 14 2012

To learn more about TRADJENTA visit: www.TRADJENTA.com. For full prescribing information visit: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Tradjenta/Tradjenta.pdf or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257.

Please report any unexpected effects or product problems to the Boehringer Ingelheim Drug Information Unit by calling 1-800-542-6257.

About Diabetes

Approximately 25.8 million Americans(2) and an estimated 366 million people worldwide(3) 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.(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 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 TRADJENTA tablets. 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 TRADJENTA will 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.

P-LLY

TJ529400PR  

(Logo: http://photos.prnewswire.com/prnh/20031219/LLYLOGO)

(Logo: http://photos.prnewswire.com/prnh/20110825/DE57898LOGO)

1. Rosenstock J, et al. American Diabetes Association, 71st Scientific Sessions, San Diego, CA, 1103-P; NCT01243424. 2011.

2. 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, Center for Disease Control and Prevention, 2011.

3. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2011.

4. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: July 27, 2012.

SOURCE Eli Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.