Data From Post-Hoc Analyses Presented at EASD Examine Safety Profile of Linagliptin in Adults with Type 2 Diabetes

   Data From Post-Hoc Analyses Presented at EASD Examine Safety Profile of
                  Linagliptin in Adults with Type 2 Diabetes

Two pooled analyses of data from clinical trials in adults with type 2
diabetes, including the elderly with normal renal function to severe renal
impairment, found similar incidence of adverse events for linagliptin compared
with placebo

PR Newswire

RIDGEFIELD, Conn. and INDIANAPOLIS, Sept. 24, 2013

RIDGEFIELD, Conn. and INDIANAPOLIS, Sept. 24, 2013 /PRNewswire/ --Boehringer
Ingelheim and Eli Lilly and Company (Lilly; NYSE: LLY) today announced results
from two post-hoc, pooled analyses of data from placebo-controlled clinical
trials, which examined the safety of the dipeptidyl peptidase-4 (DPP-4)
inhibitor linagliptin in adults with type 2 diabetes (T2D). These data were
presented at the 49^th Annual Meeting of the European Association for the
Study of Diabetes (EASD).

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). 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.

General safety analysis
Findings from a pooled, post-hoc analysis of safety data from 22 linagliptin
clinical trials with 7,400 adults with T2D (4,810 received linagliptin, 2,590
received placebo) included the following^1:

  oThe hypoglycemic incidence rate for linagliptin compared with placebo was
    11.5 percent vs. 14 percent, respectively
  oOverall incidence of adverse events (AE) or serious adverse events (SAE)
    with linagliptin was similar to placebo (AE 56.5 percent versus 61.2
    percent, and SAE 4.8 percent versus 6.3 percent, respectively)

"Drug safety is an important consideration in the selection of appropriate
treatments for adults with type 2 diabetes, as different populations often may
have drug contraindications and require dose adjustments to help manage their
disease," said Prof. Nikolaus Marx, Professor of Medicine and Cardiology,
University Hospital of Aachen, Germany. "The results presented today examine
the safety profile of linagliptin."

Renal safety data in the elderly
Results from another post-hoc analysis^2evaluated pooled data from seven
randomized, placebo-controlled phase III clinical trials including 1,293
adults with T2D who were 65 years or older showed:

  oOverall renal function, as assessed by estimated glomerular filtration
    rate (eGFR), was not significantly altered by treatment with linagliptin
    from baseline to week 24, compared with placebo (adjusted mean ± SE eGFR
    of −1.8 ± 0.7 mL/min for linagliptin vs. −1.1 ± 0.9 mL/min for placebo).
    The majority of patients in the linagliptin group had mild renal
    impairment with similar proportions of mild, moderate and severe renal
    impairment found in the placebo group.
  oRenal and urinary AEs were experienced by 5.5 percent and 4.3 percent of
    linagliptin and placebo patients, respectively
  oIncidence of investigator-defined hypoglycemia was lower in patients who
    received linagliptin compared with placebo (21.3 percent versus 24.7
    percent), with most events occurring in trials that included a
    sulfonylurea or basal insulin as background therapy
  oAcute renal failure occurred in 0.5 percent and 0.2 percent of linagliptin
    and placebo patients, respectively

"The results from these pooled analyses continued to demonstrate that
linagliptin is a treatment option for a wide range of adults with type 2
diabetes, including the elderly and those with renal impairment," said
Christophe Arbet-Engels, MD, PhD, vice president, metabolic clinical
development and medical affairs, Boehringer Ingelheim Pharmaceuticals, Inc.
"These findings provide healthcare providers with additional information they
may need to help manage the increasing number of adults with type 2 diabetes
they work with every day."

The U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA)
and several other regulatory authorities worldwide have approved linagliptin
for the treatment of adults with T2D as monotherapy or in combination with
metformin, metformin + sulfonylurea, and as add-on therapy to insulin. With
linagliptin, no dose adjustment is required regardless of declining renal
function or hepatic impairment.^3,4

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

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

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

Especially tell your doctor if you take

  oOther medicines that can lower your blood sugar, such as a sulfonylurea or

       oTRADJENTA 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.
       oSigns and symptoms of low blood sugar may include headache,
         drowsiness, weakness, dizziness, confusion, irritability, hunger,
         fast heartbeat, sweating, or feeling jittery.

  orifampin (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 or call 1-800-FDA-1088.

For more safety information, please see Medication Guide and full Prescribing


*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: For full prescribing
information visit:
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^5 and an estimated 371 million people
worldwide^6 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 or

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

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

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



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.


Catherine London
Associate Director, Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
Phone: (203) 798-4638

Tammy Hull
Communications Manager
Lilly Diabetes
Phone: (317) 651-9116


1.Lehrke M et al. Safety and tolerability of linagliptin in 7,400 patients
    with Type 2 Diabetes: A pooled comprehensive analysis of prospective
    safety reporting in placebo-controlled studies. Poster No: 986. Presented
    at the European Association for the Study of Diabetes (EASD), September
    23-27, Barcelona.
2.Patel S et al. Renal safety of linagliptin in elderly patients with Type 2
    Diabetes: analysis of pooled patient data from seven Phase III clinical
    trials. Poster No: 926. Presented at the European Association for the
    Study of Diabetes (EASD), September 23-27, Barcelona.
3.Tradjenta® (linagliptin) tablets. Highlights of Prescribing Information.
    Initial US Approval: 2011.
4.EMA. Trajenta® (linagliptin) tablets. EMA Summary of Product
    Characteristics. 2011.
5.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.
6.International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact
    Sheet. 2012.
7.International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What
    is Diabetes?
    Accessed on: July 18, 2013.
8.American Diabetes Association. Economic costs of diabetes in the U.S. in
    2012. Diabetes Care. 2013;36 (4):1033 1046.


SOURCE Eli Lilly and Company; Boehringer Ingelheim

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