Cardiovascular outcome study on Tradjenta® (linagliptin) tablets in adult patients with type 2 diabetes completes enrollment

  Cardiovascular outcome study on Tradjenta® (linagliptin) tablets in adult
              patients with type 2 diabetes completes enrollment

Head-to-head cardiovascular outcome study compares TRADJENTA with glimepiride

PR Newswire

RIDGEFIELD, Conn. and INDIANAPOLIS, Nov. 8, 2012

RIDGEFIELD, Conn. and INDIANAPOLIS, Nov.8, 2012 /PRNewswire/ --Boehringer
Ingelheim Pharmaceuticals, Inc. and  Eli Lilly and Company (NYSE: LLY) today
announced the clinical trial enrollment of patients for CAROLINA
(Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients
with Type 2 Diabetes) has been completed. Linagliptin is currently the only
DPP-4 inhibitor that is being compared to a sulfonylurea in a long-term
cardiovascular (CV) outcome study.

Linagliptin, marketed in the U.S. as Tradjenta®, is a once-daily tablet used
along with diet and exercise to improve glycemic control in adults with type 2
diabetes. TRADJENTA should not be used in patients with type 1 diabetes or for
the treatment of diabetic ketoacidosis (increased ketones in the blood or

The study includes over 6,000 patients in 43 countries at more than 600 sites
around the world. The aim of the study is to investigate and compare the
long-term impact on CV morbidity and mortality of treatment with TRADJENTA or
glimepiride over a period of about 6–7 years.(1) Additionally, the study will
compare secondary measures of efficacy with regard to lowering blood glucose
as well as safety parameters, including body weight and the incidence of
hypoglycemia in patients with type 2 diabetes at elevated cardiovascular risk
receiving usual care, and compare the outcome against glimepiride.(1)

"CAROLINA will evaluate the cardiovascular safety of linagliptin compared to
the sulfonylurea glimepiride," said Dr. Julio Rosenstock, Director of the
Dallas Diabetes and Endocrine Center at Medical City in Dallas and Principal
Investigator of the study. "Sulfonylureas are frequently used add-on therapy
to metformin, which is considered the standard first-line therapy. This is the
first time a DPP-4 inhibitor is being directly compared to a sulfonylurea in a
long-term cardiovascular outcome study."

The primary endpoint of CAROLINA will be timed to the first occurrence of
either CV death, non-fatal myocardial infarction, non-fatal stroke or
hospitalization for unstable angina pectoris.(1)^The study is expected to
complete in 2018.

"There are limited available data reporting on CV-related comorbidities with
current therapies for patients with type 2 diabetes. For the first time, this
study has the potential to compare the CV morbidity, mortality and safety of
the DPP-4 inhibitor linagliptin to the commonly prescribed sulfonylurea
glimepiride," said Christophe Arbet-Engels, MD, PhD, MBA, vice president,
metabolic-clinical development and medical affairs, Boehringer Ingelheim. "It
is our hope CAROLINA will help us to better understand the effect on
cardiovascular outcomes of linagliptin compared to glimepiride, and,
therefore, add to the knowledge base physicians use to decide how to treat
their patients."

To learn more about TRADJENTA and for full prescribing information visit:, or call Boehringer Ingelheim Pharmaceuticals, Inc. at

About CAROLINA Study Design(1)

CAROLINA evaluates the CV safety of linagliptin in comparison to glimepiride
in patients with T2D and at increased CV risk.

Inclusion criteria include at least one of the following:

  oPrevious vascular disease
  oEvidence of vascular-related end-organ damage such as albuminuria or
  oAge greater than or equal to 70 years
  oTwo or more specified traditional CV risk factors, such as hypertension or

Patients are predominantly on metformin background therapy, but the protocol
also allows patients with contraindications to metformin, e.g., due to renal
impairment, to participate. Linagliptin 5 mg is being compared to glimepiride
1–4 mg, both as monotherapy or as add-on therapy to metformin or
alpha-glucosidase inhibitors in at least 6,000 patients with a 6–7 year

What are TRADJENTA (linagliptin) 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).

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 are rash, 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

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 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
breastfeeding or plan to breastfeed.

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 or call 1-800-FDA-1088.

For more safety information, please see Patient Information and full
Prescribing Information.

TJ CONS ISI August 14 2012

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(2) and an estimated 366 million people
worldwide(3) 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 disease that occurs when the body either does
not properly produce, or use, the hormone insulin.(4)

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 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 or

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 and
follow us on Twitter at

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

For more information, visit

This press release contains forward-looking statements about TRADJENTA
tablets. 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.





1.Rosenstock J, et al. American Diabetes Association, 71st Scientific
Sessions, San Diego, CA, 1103-P; NCT01243424. 2011.

2.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.

3.International Diabetes Federation. Diabetes Atlas, 5th Edition: Fact Sheet.

4.International Diabetes Federation. IDF Diabetes Atlas, 5th Edition: What is
Diabetes? Accessed on:
July 27, 2012.

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

Contact: Catherine London, Associate Director, Communications and Public
Relations, Boehringer Ingelheim Pharmaceuticals, Inc., +1-203-798-4638,; Tammy Hull, Communications Manager, Lilly
Diabetes, +1-317-651-9116,
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