Linagliptin Demonstrated Significant HbA1c Reduction in Elderly People With Type 2 Diabetes With Inadequate Glycemic Control

Ridgefield, Conn. and Indianapolis, August 15, 2013 – Data published in The Lancet showed that elderly people with type 2 diabetes (T2D) treated for 24 weeks with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (TRADJENTA^®), marketed by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (Lilly; NYSE: LLY), experienced significant reductions in blood glucose levels (HbA1c) compared with those receiving placebo. In addition, the overall safety and tolerability profile of linagliptin was similar to placebo.¹

Linagliptin, which is marketed as TRADJENTA^® (linagliptin) tablets in the U.S., is a once-daily 5-mg tablet used along with diet and exercise to improve glycemic control in adults with T2D. 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). TRADJENTA has not been studied in patients with a history of pancreatitis and it is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using TRADJENTA.

“Elderly individuals represent approximately 15 percent of people with type 2 diabetes worldwide,²” said Professor Anthony H. Barnett, MD, FRCP, Heart of England NHS Foundation Trust and University of Birmingham, United Kingdom. “This study may help inform treatment decisions for improving glycemic control in the elderly.”

The publication reports on a 24-week, double-blind, parallel-group, multinational, phase III study in 241 elderly people (≥70 years; mean age, 74.9 years) with T2D randomized to receive linagliptin 5 mg (n=162) or placebo (n=79), in addition to existing glucose-lowering drugs (i.e. metformin and/or sulfonylurea and/or basal insulin). The primary endpoint was change in HbA1c from baseline (7.8 percent for linagliptin versus 7.7 percent for placebo) to week 24. Key results from the study showed that the mean change from baseline in HbA1c with linagliptin was −0.64 percent (p<0.0001) after 24 weeks, which showed superiority versus placebo, adjusted for a mean 0.04 percent HbA1C increase for placebo. In addition, analysis of a secondary endpoint showed that the placebo-adjusted mean reduction in fasting plasma glucose from baseline with linagliptin was −20.7 mg/dL (−1.15 mmol/L; p<0.0001).

The percentage of people with any adverse event was the same in both treatment groups (75.9 percent). Common adverse events included hypoglycemia (low blood glucose; 22.8 percent and 16.5 percent for linagliptin and placebo, respectively), nasopharyngitis (common cold; 10.5 percent in the linagliptin arm and 8.9 percent on placebo), diarrhea (5.6 percent in the linagliptin arm and 2.5 percent on placebo), hyperglycemia (high blood glucose; 5.6 percent and 10.1 percent for linagliptin and placebo, respectively), back pain (7 percent for linagliptin), fall (4.3 percent and 2.5 percent for linagliptin and placebo, respectively) and urinary tract infection (4.3 percent in the linagliptin arm and 6.3 percent on placebo). One patient per group had a drug-related adverse event leading to discontinuation of the study. Investigator-defined hypoglycemia occurred in 24.1 percent of the linagliptin group and 16.5 percent of the placebo group.

“Elderly people with type 2 diabetes have different challenges managing their blood sugar levels,” said Christophe Arbet-Engels, MD, PhD, vice president, metabolic clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “This study shows linagliptin may help to reduce blood sugar levels in elderly people with inadequately controlled diabetes, and adds to the growing body of evidence for the safety and efficacy profile for linagliptin in this population.”

About the study
The study was conducted at 33 centers in five countries (Australia, Canada, Denmark, The Netherlands and Sweden). A total of 241 people who were ≥70 years with T2D, had HbA1c of ≥7.0 percent and received metformin and/or sulfonylurea and/or basal insulin were randomized 2:1 to once-daily oral treatment with linagliptin 5 mg or placebo for 24 weeks.

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 U.S. 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

*The brands listed are trademarks of their respective owners and are not trademarks of Boehringer Ingelheim Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Boehringer Ingelheim Pharmaceuticals, Inc., or its products.

To learn more about TRADJENTA visit: www.TRADJENTA.com. For full prescribing information visit: https://content.boehringer-ingelheim.com/DAM/60f7a616-66fd-4405-a275-af1e01211cc5/tradjenta-us-pi.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 Americans⁶ and an estimated 371 million people worldwide³ 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.⁶ Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin.⁴ Diabetes was estimated to cost the U.S. $245 billion in 2012.⁵

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.

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 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% 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.

P-LLY
TJ573300

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.

Lilly Media Contact
Tammy Hull
Communications Manager
Lilly Diabetes
Phone: (317) 651-9116
e-mail

References

1. Barnett A et al. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. The Lancet. Published on line August 13, 2013.
2. Merck Manuals. Hormonal and Metabolic Disorders; Diabetes Mellitus. http://www.merckmanuals.com/home/hormonal_and_metabolic_disorders/diabetes_mellitus_dm/diabetes_mellitus.html. Accessed on: August 6, 2013.
3. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2012.
4. International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: July 18, 2013.
5. American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013;36(4):1033-1046.
6. 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