News Release

RIDGEFIELD, Conn. and INDIANAPOLIS, June 25, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results from a new pooled analysis of phase III data for the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin. The post-hoc meta-analysis, presented at the American Diabetes Association 73rd Scientific Sessions^®, compared the incidence of cardiovascular (CV) events with linagliptin for the treatment of adults with type 2 diabetes (T2D) with the incidence of CV events for a number of comparators (placebo, glimepiride and voglibose).¹

People with T2D have a significantly elevated risk for heart attack, stroke and other CV events, compared with the general population. A second abstract published in the ADA's abstract book for the conference highlights the characteristics of people with T2D at high CV risk or with CV complications enrolled in the CAROLINA (CARdiovascular Outcome Study of LINAgliptin versus Glimepiride in Early Type 2 Diabetes) study. This study is investigating the long-term CV safety of linagliptin compared to glimepiride and to evaluate their effects on CV outcomes in these high-risk patients.  

"There is a well-established association between cardiovascular events and type 2 diabetes," said Professor Odd-Erik Johansen, senior clinical program leader, Boehringer Ingelheim. "In fact, cardiovascular events rank as the major cause of death in patients with diabetes, accounting for more than 65 percent of all diabetes fatalities.³ It is, therefore, important to evaluate treatments within this context in order to inform clinical decision-making when selecting a therapy in type 2 diabetes."

About the Pooled Analysis
For the post-hoc analysis, researchers pooled results from 19 double-blind studies, including data from 9,459 patients treated with either linagliptin (5mg: 5,687, 10mg: 160) or a comparator group of placebo and other oral antihyperglycemic treatments (placebo: 2,675, glimepiride: 775, voglibose: 162). The cumulative patient exposure (the total length of time all patients had been exposed to treatment) was 4,421 patient-years in the linagliptin group and 3,255 patient-years in the comparator group. The primary endpoint of the pooled analysis was a composite of CV death, non-fatal stroke, non-fatal myocardial infarction (MI) and hospitalization for unstable angina pectoris (UAP). CV events were prospectively adjudicated by a blinded independent expert committee.

The post-hoc meta-analysis showed a lower incidence rate of the composite CV endpoint for the linagliptin group (13.4 per 1,000 patient years), versus the comparator group (18.9 per 1,000 patient years), and a hazard ratio of 0.78 (CI: 0.55, 1.12, p=NS).¹

About CAROLINA
CAROLINA is evaluating the long-term impact of treatment with linagliptin and glimepiride on CV death and disability, and is the only ongoing long-term CV outcome trial of a DPP-4 inhibitor versus a single active comparator (glimepiride). The baseline patient characteristics for the study patients (n=6,103), published in the ADA Scientific Sessions Abstract book, showed that the recruited patient population is reflective of the target population with early type 2 diabetes and an increased risk for CV events.² Results from the double-blind, active controlled, event-driven trial are expected in 2018. 

The CAROLINA baseline patient characteristics include the following:²

• 33.7 percent have previous CV complications 
• 41 percent have diabetes for less than five years; 28 percent have diabetes for up to 5-10 years  
• 72.5 percent have a baseline HbA_1c &#60 7.5 percent 
• 67.3 percent were on one glucose-lowering agent; 22.3 percent were on two agents  
• 89.1 percent of patients on monotherapy receiving metformin 
• 46 percent are obese (BMI≥30 kg/m²) 
• 84.2 percent are on an antihypertensive therapy; 60 percent are on a statin; 47.5 percent are on aspirin

Linagliptin, which is marketed as Tradjenta® (linagliptin) tablets in the U.S., is a once-daily 5mg tablet used along with diet and exercise to improve glycemic 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). If you have had inflammation of the pancreas (pancreatitis) in the past, it is not known if you have a higher chance of getting pancreatitis while you take TRADJENTA. Linagliptin is a DPP-4 inhibitor that does not require dose adjustments, regardless of declining renal function or hepatic impairment. There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRADJENTA or any other antidiabetic drug.

What are TRADJENTA 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).

If you have had inflammation of the pancreas (pancreatitis) in the past, it is not known if you have a higher chance of getting pancreatitis while you take TRADJENTA.

Important Safety Information

What is the most important information I should know about TRADJENTA?
Serious side effects can happen to people taking TRADJENTA, including inflammation of the pancreas (pancreatitis), which may be severe and lead to death. Before you start taking TRADJENTA, tell your doctor if you have ever had pancreatitis, gallstones, a history of alcoholism, or high triglyceride levels.

Stop taking TRADJENTA and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

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 may include rash, itching, flaking or peeling; raised red patches on your skin (hives); swelling of your face, lips, tongue 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 using TRADJENTA?
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. TRADJENTA may affect the way other medicines work, and other medicines may affect how TRADJENTA works.

Especially 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. 
• rifampin (Rifadin®, Rimactane®, Rifater®, Rifamate®), an antibiotic that is used to treat tuberculosis.

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

What are the possible side effects of TRADJENTA?
The most common side effects of TRADJENTA include stuffy or runny nose, sore throat, cough and diarrhea.

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 Medication Guide and full Prescribing Information.

TJ CONS ISI 19JUNE2013

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 Americans³ and an estimated 371 million people worldwide⁴ 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 condition that occurs when the body does not properly produce or use the hormone insulin.⁵ Diabetes was estimated to cost the U.S. $245 billion in 2012.⁶

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 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
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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.

As a central element of its culture, Boehringer Ingelheim has a demonstrated commitment to corporate social responsibility. 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 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5 percent of its net sales.

For more information please visit www.us.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 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.

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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 commercialization. There is no guarantee that future study results and patient experience will be consistent with study findings to date or that linagliptin 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.

CONTACT:
Catherine London
Associate Director, Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
Email: usnews@boehringer-ingelheim.com
Phone: (203) 798-4638

Tammy Hull
Communications Manager
Lilly Diabetes
Email: hullta@lilly.com 
Phone: (317) 651-9116

References 

1. Johansen OE, et al. Cardiovascular (CV) safety of linagliptin in patients with type 2 diabetes (T2D): A pooled comprehensive analysis of prospectively adjudicated CV events in Phase 3 studies. Oral No: 376-OR. Presented at the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL. 
2. Marx N, et al. Baseline characteristics of participants enrolled in the CARdiovascular Outcome Study of LINAgliptin Versus Glimepiride in Early Type 2 Diabetes (CAROLINA). Published in the abstract book for the American Diabetes Association (ADA) 73rd Scientific Sessions®. June 21-25, Chicago, IL. 
3. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and pre-diabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Center for Disease Control and Prevention, 2011.
4. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2012. 
5. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: June 17, 2013.
6. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033-1046.

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SOURCE Eli Lilly and Company; Boehringer Ingelheim