News Release

RIDGEFIELD, Conn. and INDIANAPOLIS, June 22, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results from two phase III clinical studies that showed linagliptin in Asian adults, as monotherapy and in combination with metformin, improved blood glucose control in people with type 2 diabetes (T2D) from China, Malaysia and the Philippines. The study data from two randomized phase III clinical trials were presented at the American Diabetes Association 73rd Scientific Sessions^®.

In Asia, the rate of T2D is rapidly increasing. If the current trend continues, it is estimated that more than 60 percent of the world's diabetes population will be in Asia by 2030.¹ Similarly, in the United States, the rate of T2D in Chinese Americans is much higher than the rate in the Chinese population living in rural China.² A combination of both genetic and environmental influences is attributed to the higher rate of T2D in people of Asian descent.²

"The results of these two studies continue to support use of linagliptin in Asian adults with type 2 diabetes," said Christophe Arbet-Engels, MD, PhD, MBA, vice president, metabolic-clinical development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Adults of Asian descent with type 2 diabetes tend to develop the condition at a younger age than those from Western populations, regardless of their body weight." ¹

In the first study, linagliptin monotherapy demonstrated a 0.68 percent reduction in HbA_1c (from a mean baseline HbA_1c of 7.95 percent) at 24 weeks among Asian patients from China, Malaysia, and the Philippines, compared with a reduction of 0.18 percent (from a mean baseline HbA_1c of 8.09 percent) in the placebo group (placebo-corrected difference of -0.50 percent; 95 percent confidence interval [CI]: -0.71, -0.28; p &#60 0.0001). In a pre-defined subgroup of patients with a baseline HbA_1c of at least 8.5 percent, treatment with linagliptin resulted in a placebo-adjusted reduction in HbA_1c of 0.91 percent (p &#60 0.0001) at 24 weeks.³ HbA_1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months.³

Results from the second study showed an HbA_1c reduction of 0.66 percent (from a mean baseline HbA_1c of 7.99 percent) at 24 weeks among Asian patients from China, Malaysia, and the Philippines who received linagliptin added to metformin at 24 weeks, versus a reduction of 0.14 percent (from a mean baseline HbA_1c of 8.00 percent) among patients receiving placebo added to metformin (placebo-corrected difference in HbA_1c was -0.52 percent; 95 percent CI: -0.70, -0.34; p &#60 0.0001).^[4]

In both studies, the incidence of adverse events (AEs) was similar in each treatment group compared with placebo. The incidence of AEs for linagliptin were 28.0 percent in the monotherapy study and 27.3 percent in the add-on therapy study, and comparable to the placebo arm (28.3 percent and 28.0 percent, respectively). In the monotherapy study, drug-related AEs were reported in 3.0 percent of linagliptin patients and 2.0 percent of placebo patients; in the add-on trial, drug-related AEs were reported in 2.4 percent of linagliptin patients and 0.0 percent of placebo patients. In addition, investigator-defined hypoglycemia occurred in 0.5 percent of linagliptin patients and 0.0 percent of placebo patients in the monotherapy study, and in 1.0 percent of patients in both groups of the add-on study.^{3, 4}

About the Studies
The first study was a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of linagliptin monotherapy for 24 weeks in Asian patients with inadequately controlled type 2 diabetes mellitus. The study included a total of 300 patients with T2D from China (n=261), Malaysia (n=22) and the Philippines (n=17). Patients who were treatment naïve or who had been treated with one antihyperglycemic drug were randomized to either linagliptin 5 mg daily or placebo following a 4-week washout period of prior drugs. The primary endpoint was change from baseline in mean HbA _1c after 24 weeks.³ Mean HbA_1c levels at baseline were 7.95 percent for patients in the linagliptin group and 8.09 percent for patients in the placebo group.

The second study, also a randomized, double-blind, placebo-controlled trial, evaluated the efficacy and safety of linagliptin as add-on therapy to metformin in Asian patients with inadequately controlled type 2 diabetes mellitus. The study included a total of 306 patients with T2D from China (n=265), Malaysia (n=17) and the Philippines (n=24). Antihyperglycemic drugs other than metformin were washed out for 4 weeks prior to randomization to either linagliptin 5mg daily or placebo added to metformin. The primary endpoint of the study was change from baseline in mean HbA_1c after 24 weeks.⁴ Mean HbA _1c levels at baseline were 7.99 percent for patients in the linagliptin group and 8.00 percent for patients in the placebo group.

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 patients have had pancreatitis in the past, it is not known if they have a higher chance of getting pancreatitis while taking linagliptin. Linagliptin is a DPP-4 inhibitor that does not require dose adjustments, regardless of declining renal function or hepatic impairment.

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 Americans⁵ and an estimated 371 million people worldwide⁶ 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.⁵ Diabetes is a chronic condition that occurs when the body does not properly produce or use the hormone insulin.⁷ Diabetes was estimated to cost the U.S. $245 billion in 2012.⁸

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 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.

P-LLY
TJ552414PR

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, Communications and 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. Ramachandran A, et al. Trends in prevalence of diabetes in Asian countries. World J Diabetes. 2012; 3(6): 110—117.
2. Asian American Diabetes Initiative. Joslin Diabetes Center, Boston, MA. http://aadi.joslin.org/content/diabetes-asians-asian-americans. Accessed on: April 9, 2013.
3. Chen Y, et al. Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: a 24-week, randomized, Phase III clinical trial: Poster No. 1159-P. Presented at the American Diabetes Association 73rd Scientific Sessions®. June 21-25, Chicago, IL.
4. Wang W, et al. Efficacy and safety of linagliptin in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin: a 24-week, randomized, Phase III clinical trial: Poster No. 1177-P. Presented at the American Diabetes Association 73rd Scientific Sessions®. June 21-25, Chicago, IL
5. 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.
6. International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2012.
7. 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.
8. 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 Pharmaceuticals, Inc.