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Boehringer Ingelheim Corporation and Eli Lilly Canada Inc. (LLY) Present New linagliptin Data at American Diabetes Association's 72nd Scientific Sessions®  
6/11/2012 11:00:59 AM

RIDGEFIELD, Conn. and INDIANAPOLIS, June 9, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company(NYSE: LLY) presented results from two randomized phase 3 clinical trials and a post-hoc analysis for linagliptin at the American Diabetes Association's (ADA's) 72nd Scientific Sessions®. The new studies provide additional data evaluating the efficacy and safety of linagliptin (alone or in combination with other diabetes therapies) in adults with type 2 diabetes.[1],[2],[3] Linagliptin, marketed in the U.S. as Tradjenta®, is a once-daily tablet that is used along with diet and exercise to improve glycemic control in adults with type 2 diabetes.[4]

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 combination with insulin.

"Patients with type 2 diabetes often need more than one therapy to improve their glycemic control," said Dr. Lance A. Sloan, MD, FACE, President and Chief Medical Officer, Texas Institute for Kidney and Endocrine Disorders. "These new studies provide additional data further evaluating the efficacy and safety of linagliptin, alone or in combination, in adults with type 2 diabetes who have experienced insufficient glycemic control on other treatments."

Interim results of the first phase 3 study presented here (abstract #999-P) showed that adding linagliptin to a background of basal insulin alone or in combination with metformin and/or pioglitazone demonstrated a placebo-adjusted reduction in hemoglobin A1c (HbA1c or A1C) of 0.65 percent from a baseline A1C of 8.3 percent[1] at 24 weeks versus adding placebo to these background therapies in adult patients with type 2 diabetes. A1C is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months.

In a second phase 3 study (abstract #1017-P), linagliptin showed a 0.64 percent placebo-adjusted reduction in A1C (p<0.0001) at 24 weeks from baseline (A1C = 7.8 percent) in elderly patients (mean age 74.9 years) insufficiently controlled despite previous treatment with metformin and/or sulfonylurea and/or insulin therapy. Hypoglycemia occurred in 24.1 percent of patients on linagliptin versus 16.5 percent of patients on placebo.[2]

The third abstract was a post-hoc analysis (abstract #1044-P) in which patients with uncontrolled A1C on a background of metformin were randomized to add-on linagliptin or glimepiride. The endpoint of the 104-week exploratory analysis was to assess the proportions achieving a glycemic target A1C <7 percent without weight gain (defined as <1 kg increase in body weight vs baseline) and without hypoglycemia. After 104 weeks of treatment, both linagliptin and glimepiride reduced mean A1C levels by 0.6 percent from baseline (baseline: 7.2 percent linagliptin, 7.3 percent glimepiride) and 76 percent of patients in both groups achieved target A1C <7 percent. Analyses were based on a per protocol population on treatment after 104 weeks without the use of rescue medication. Fewer patients taking linagliptin versus glimepiride experienced hypoglycemia (very low blood sugar levels) and weight gain during the trial period (6 percent versus 42 percent and 22 percent versus 55 percent, respectively).[3] A significantly higher proportion in the linagliptin group than the glimepiride group achieved the composite endpoint (54 percent versus 23 percent, respectively).

Abstract 999-P Study Design and Safety

This 52-week, multicenter, randomized, placebo-controlled phase 3 study evaluated the efficacy and safety of linagliptin as an add-on therapy to basal insulin alone, or in combination with metformin and/or pioglitazone in adult patients with type 2 diabetes. The study included 1,261 patients who had inadequate glycemic control with a stable dose of basal insulin with or without metformin and/or pioglitazone (i.e., insulin glargine, insulin detemir or NPH insulin).[1] Patients were randomized to receive either 5 mg of linagliptin or placebo once daily. The primary efficacy endpoint was the mean change in A1C from baseline to week 24, during which time the basal insulin and metformin and/or pioglitazone dose remained stable.[1]

The overall frequency of adverse events (linagliptin, 71.8 percent versus placebo, 72.5 percent) and hypoglycemia (linagliptin, 25.7 percent versus placebo, 27.3 percent) were similar in both groups.(1) In addition, body weight did not significantly change from baseline (-0.17 kg +/- 0.11 versus +0.13 kg +/- 0.12; p=0.07) in the linagliptin and placebo groups, respectively.[1]

Abstract 1017-P Study Design and Safety

This randomized, placebo-controlled, double-blind phase 3 study evaluated the efficacy and safety of linagliptin 5 mg daily in 241 elderly patients (74.9 years +/- 4.3 years) with type 2 diabetes, who had insufficient glycemic control despite treatment with metformin, sulfonylurea and/or insulin therapy. Patients were randomized to receive either 5 mg of linagliptin once daily, or placebo as an add-on to stable background therapy over 24 weeks.[2] Patients were taking either metformin (84.9 percent), sulfonylurea (57.6 percent) or insulin therapy (21.0 percent). Baseline A1C was 7.8 percent and 7.7 percent in the linagliptin and placebo groups, respectively.[2] Drug-related adverse events were experienced by 21.0 percent and 13.9 percent of linagliptin and placebo patients, respectively. Hypoglycemia occurred in 24.1 percent and 16.5 percent, respectively (p=0.1625).[2]

Abstract 1044-P Study Design and Safety

An exploratory analysis of a 104-week study assessed the proportions of adult patients with type 2 diabetes treated with linagliptin versus glimepiride both on a background of metformin who achieved a glycemic target of A1C <7 percent without weight gain (defined as <1kg increase in body weight versus baseline) and without hypoglycemia (defined event per protocol).[3]

Analyses were based on a per-protocol population on treatment after two years without the use of rescue medication (according to fasting plasma glucose and A1C thresholds). A total of 504 patients were evaluable (233 linagliptin; 271 glimepiride). Baseline A1C levels were similar in the two groups (linagliptin, 7.2 percent and glimepiride, 7.3 percent).[3] Six percent of linagliptin patients experienced hypoglycemia versus 22 percent on glimepiride and 22 percent experienced weight gain, versus 55 percent on glimepiride. Consequently, a significantly higher proportion in the linagliptin group than with the glimepiride group achieved the composite endpoint (54 percent versus 23 percent, respectively).

TRADJENTA is the first member of the dipeptidyl peptidase-4 (DPP-4) inhibitor class to be approved at one dosage strength. Among many considerations when treating patients with type 2 diabetes, approximately 40 percent of individuals have some degree of renal impairment.[5] With TRADJENTA, no dose adjustment is required regardless of declining renal function or hepatic impairment.[4] 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.

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).

It is not known if TRADJENTA is safe and effective when used with insulin.

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 arerash, 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 medicine 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 breast-feeding or plan to breast-feed.

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.

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[6] and an estimated 366 million people worldwide[7] 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 disease that occurs when the body either does not properly produce, or use, the hormone insulin.[8]

Boehringer Ingelheim and Eli Lilly and Company

In January 2011, Boehringer Ingelheim and Eli Lilly and Companyannounced 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 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 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

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[1] Yki-Jarvinen H, Duran-Garcia S, Pinnetti S, et al. Efficacy and Safety of Linagliptin as Add-On Therapy to Basal Insulin in Patients With Type 2 Diabetes. Abstract #999-P. Presented at the American Diabetes Association's (ADA's) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.

[2] Barnett A, Huisman H, Jones R, et al. Efficacy and Safety of Linagliptin in Elderly Patients (70 Years) With Type 2 Diabetes. Abstract #1017-P. Presented at the American Diabetes Association's (ADA's) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.

[3] Gallwitz B, Rosenstock J, Emser A, et al. Linagliptin is More Effective than Glimepiride at Achieving a Composite Outcome of A1C Target with No Hypoglycemia and No Weight Gain over two Years in Mildly Hyperglycemic Type 2 Diabetes Patients on Metformin. Abstract #1044-P. Presented at the American Diabetes Association's (ADA's) 72nd Scientific Sessions®. June 8-12, Philadelphia, PA.

[4] Tradjenta® (linagliptin) tablets. Highlights of Prescribing Information. Initial US Approval: 2011.

[5] Plantinga LC, Crews DC, Coresh J; CDC CKD Surveillance Team. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol. 2010;5:673-682.

[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.

[7] International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet. 2011.

[8] International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is Diabetes? http://www.idf.org/diabetesatlas/5e/what-is-diabetes. Accessed on: April 11, 2012.

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


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