Results of new exploratory analyses assessing the incidence of hypoglycemia with linagliptin in adults with type 2 diabetes announced

RIDGEFIELD, Conn. and INDIANAPOLIS, June 22, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results from two exploratory analyses assessing the risk of hypoglycemia with linagliptin treatment in adults with type 2 diabetes (T2D).^{1, 2}

In an exploratory analysis of data from two phase III trials, elderly people with T2D (mean age 74 years) treated with linagliptin as add-on to stable basal insulin regimen trended towards a 37 percent and 34 percent lower occurrence of overall hypoglycemia (odds ratio [OR] 0.63 [95 percent confidence interval [CI]: 0.37- 1.10]) and confirmed hypoglycemia (0.66 [0.36-1.21]), respectively, compared with people treated with placebo as add-on to basal insulin.¹ Overall hypoglycemia included all investigator-defined hypoglycemic events, while confirmed hypoglycemia was defined as blood glucose levels at or below 70 mg/dL.

In a separate exploratory analysis of two-year data from a phase III trial comparing linagliptin to glimepiride, fewer people treated with the DPP-4 inhibitor linagliptin versus the sulfonylurea glimepiride experienced hypoglycemia (7.5 percent vs. 36.1 percent; p<0.0001).² After excluding events during dose escalation of glimepiride (1-4 mg in weeks 0-16), a difference in those reporting hypoglycemia still remained present (5.9 percent vs. 25.8 percent; p<0.0001). The difference in the incidence of hypoglycemia between linagliptin and glimepiride was observed at all time points tested, all dose levels, and regardless of change from baseline in HbA_1c.² Hypoglycemia in this analysis was defined as any investigator-reported hypoglycemic event.

At weeks 4, 8, 12, 16 and 104, the percentage of people who experienced a hypoglycemic event was higher with glimepiride versus linagliptin in each quartile of HbA_1c change from baseline (all p<0.0001). The percentage of people who experienced hypoglycemia was not increased with greater reductions in HbA_1c in either group. In all four-week intervals, the percentage of people who experienced a hypoglycemic event was lower with linagliptin versus glimepiride.¹

About the Studies
Findings from the first exploratory analysis of data on elderly people with T2D (n=247; mean age, 74 years; baseline HbA_1c, 8.2 percent) who had linagliptin or placebo added onto basal insulin therapy (baseline dose 36 U/day) from two phase III studies of 24 and > 52 weeks. The analysis measured the relative ORs for overall and confirmed hypoglycemia (the latter defined as blood glucose < 70 mg/dL). The insulin doses did not change notably throughout the trials.¹

The findings from the second analysis are based on two-year data from a randomized, double-blind study of linagliptin 5 mg qd (n=777) versus glimepiride 1 mg to 4 mg qd (n=775) in people with T2D previously uncontrolled with metformin therapy.² The study showed comparable reductions in HbA_1c between the two treatments.² For the exploratory analysis, the risk of investigator-reported hypoglycemia for linagliptin was compared with glimepiride based on dose, over time, and by HbA_1c reduction. People randomized to glimepiride started treatment on 1 mg. Those who did not achieve a fasting plasma glucose level of 110 mg/dL at 4 weeks and who were not at hypoglycemia risk were subsequently uptitrated stepwise up to a maximum of 4 mg qd.²

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 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 adjustment, 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 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

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