Full data from CAROLINA® outcome trial support long-term cardiovascular safety profile of Trajenta®

• CAROLINA^® demonstrated no increased cardiovascular risk for
  Trajenta^® (linagliptin) versus glimepiride in the only
  active-comparator cardiovascular outcome trial for a dipeptidyl
  peptidase-4 (DPP-4) inhibitor
• Adults with diabetes treated with Trajenta^® experienced
  significantly fewer events of hypoglycaemia and a modest weight
  reduction compared to patients treated with glimepiride
• Detailed results from CAROLINA^® were presented at the
  American Diabetes Association’s 79th Scientific Sessions

INGELHEIM, Germany & INDIANAPOLIS, US–(BUSINESS WIRE)–Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced
full data from the CAROLINA^® trial demonstrating that Trajenta^®
(linagliptin) did not increase cardiovascular risk compared to
glimepiride in adults with type 2 diabetes and cardiovascular risk.¹
The findings were reported today at the American Diabetes Association’s
79th Scientific Sessions in San Francisco.

The trial met its primary endpoint, defined as non-inferiority for
linagliptin versus glimepiride in time to first occurrence of
cardiovascular death, non-fatal myocardial infarction or non-fatal
stroke (3P-MACE), which occurred in 11.8 percent (356 people) of the
linagliptin group compared to 12.0 percent (362 people) of the
glimepiride group.¹ The overall safety profile of linagliptin
in CAROLINA^® was consistent with previous data, and no new
safety signals were observed.^1,2

The study assessed linagliptin safety over the longest period ever
studied in a DPP-4 inhibitor cardiovascular outcome trial, with a median
follow-up of more than 6 years.¹ Linagliptin was similar to
glimepiride in the secondary endpoint of 3P-MACE plus hospitalisation
for unstable angina (4P-MACE – 13.2 percent for linagliptin versus 13.3
percent for glimepiride).¹

In CAROLINA^®, a higher proportion of patients within the
linagliptin group (16.0 percent) achieved the secondary composite
efficacy endpoint of treatment sustainability versus the glimepiride
group (10.2 percent).^*1 Compared with glimepiride,
linagliptin demonstrated similar overall effects on HbA1c, but
significantly reduced the relative risk for hypoglycaemia (low blood
sugar) by 77 percent (10.6 percent of patients treated with linagliptin
experienced any hypoglycaemic incident versus 37.7 percent for
glimepiride).¹ This risk reduction was consistent and
significant across all hypoglycaemia categories, including severe
hypoglycaemia and those requiring hospitalisation. Linagliptin was also
associated with a modest weight reduction of 1.5 kg versus glimepiride.¹

“CAROLINA^® is unique in that it is the only DPP-4 inhibitor
cardiovascular outcome trial with an active comparator,” said Waheed
Jamal, MD, Corporate Vice President and Head of Cardiovascular &
Metabolic Medicine, Boehringer Ingelheim. “When additional
glucose-lowering is needed, DPP-4 inhibitors and sulfonylureas continue
to be frequently used as add-on therapies to metformin. These data can
further support physicians in choosing the most appropriate
glucose-lowering treatment for each individual patient.”

“The American Diabetes Association and European Association for the
Study of Diabetes recommend type 2 diabetes treatments with proven
cardiovascular benefits for patients with established cardiovascular
disease,” said Jeff Emmick, M.D., Ph.D., Vice President, Product
Development, Lilly Diabetes. “But, physicians considering additional
therapies to lower blood glucose for their patients need a DPP-4
inhibitor with an established long-term safety profile. These new data
from CAROLINA^®, along with data from the placebo-controlled
cardiovascular outcome trial CARMELINA^®, expand the evidence
and experience with linagliptin, to provide healthcare professionals
with confidence in the long-term safety profile across a broad range of
patients with type 2 diabetes.”

About CAROLINA^®
CAROLINA^®
(CARdiovascular Outcome study of LINAgliptin versus glimepiride in
patients with type 2 diabetes) is a multi-national, randomised,
double-blind, active-controlled clinical trial that involved 6,033
adults with type 2 diabetes from 43 countries at more than 600 sites
observed for a median duration of more than 6 years.^3,4 The
trial included adults with early type 2 diabetes: adults with a median
disease duration of 6.2 years, who either received no treatment at all,
or received 1-2 glucose lowering agents (e.g. metformin).⁴ It
was designed to assess the effect of Trajenta^® (linagliptin)
(5 mg once daily) compared to the sulphonylurea glimepiride (both added
to stable background glucose-lowering medication and cardiovascular
standard of care) on cardiovascular safety in adults with type 2
diabetes and increased cardiovascular risk or established cardiovascular
disease.^3,4 These people reflect patients that doctors
typically see in their daily clinical practice.⁵

CAROLINA^® was led by an academic trial steering committee and
Boehringer Ingelheim and Eli Lilly and Company. CAROLINA^® is
the only DPP-4 inhibitor, active-comparator cardiovascular outcome trial.

About Trajenta^® (linagliptin)
Trajenta^®
is a one dose, once daily DPP-4 inhibitor that provides significant
efficacy in the reduction of blood sugar levels for adults with type 2
diabetes. It can be prescribed for adults with type 2 diabetes
regardless of age, disease duration, ethnicity, body mass index (BMI),
liver and kidney function.² Trajenta^® has the
lowest kidney excretion rate of all DPP-4 inhibitors.^6-9

About our cardiovascular outcome trials
Cardiovascular
outcome trials are highly relevant, as cardiovascular disease is a major
complication and the leading cause of death in type 2 diabetes.
Worldwide, most people with type 2 diabetes die of a cardiovascular
event.¹⁰ In 2015, Boehringer Ingelheim and Eli Lilly and
Company announced results from the landmark cardiovascular outcome trial
EMPA-REG OUTCOME^® with the SGLT2 inhibitor, empagliflozin,
which reduced the relative risk of cardiovascular death by 38 percent in
adults with type 2 diabetes and established cardiovascular disease, on
top of standard of care.^†‡11-13 As a result, empagliflozin
was the first oral type 2 diabetes medicine to have either a
cardiovascular indication or data on the reduction of the risk of
cardiovascular death included in the label in many countries.^11,12

CAROLINA^® is one of two cardiovascular outcome trials with
the DPP-4 inhibitor, linagliptin.^3,4 CAROLINA^® and
the CArdiovascular safety and Renal Microvascular outcomE with
LINAgliptin in patients with type 2 diabetes at high vascular risk trial
(CARMELINA^®)^14,15 provide one of the most
comprehensive datasets on the long-term safety of a DPP-4-inhibitor.

CARMELINA^® is a multi-national, randomised, double-blind,
placebo-controlled clinical trial that involved 6,979 adults with type 2
diabetes from 27 countries at more than 600 sites observed for a median
duration of 2.2 years.^14,15 CARMELINA^® studied the
impact of Trajenta^® (linagliptin) on cardiovascular and
kidney safety in adults with type 2 diabetes at high risk for heart
and/or kidney disease.^14,15 The trial met its primary
endpoint,^§ with linagliptin demonstrating a similar
cardiovascular safety profile compared to placebo when added to standard
of care.¹⁴ CARMELINA^® also included a key
secondary composite endpoint,^** showing a similar kidney
safety profile compared to placebo.¹⁴ The overall safety
profile of linagliptin in CARMELINA^® was
consistent with previous data and no new safety signals were observed.^2,14
CARMELINA^® also showed a similar rate of hospitalisation for
heart failure for linagliptin compared to placebo.¹⁴

To learn more about CAROLINA^® and CARMELINA^®,
please visit: https://www.carmelinatrial.com/

Please click on the following link for ‘Notes to Editors’ and
‘References’:

http://www.boehringer-ingelheim.com/press-release/CAROLINA-full-data

^* Secondary composite efficacy outcome defined as HbA1c at or
below 7 percent at the final visit without rescue medication, moderate
or severe hypoglycaemia or a 2 percent or greater weight gain.
^†
Adult patients with type 2 diabetes and coronary artery disease,
peripheral artery disease, or a history of MI or stroke
^‡
Standard of care included cardiovascular medications and blood sugar
lowering agents given at the discretion of physicians
^§
Primary endpoint defined as time to first occurrence of the 3P-MACE
(cardiovascular death, non-fatal myocardial infarction or non-fatal
stroke)
^** Key secondary endpoint defined as time to
first occurrence of sustained end stage kidney disease (ESKD), death due
to kidney disease, or a sustained decrease in eGFR from baseline of ≥40
percent compared to placebo

Contacts

Tetsu Owari
Media & PR
Boehringer Ingelheim
Email:
[email protected]
Phone:
+49 (6132) 77 184867

Stephan Thalen
Global Business Communications
Lilly
Diabetes
Email: [email protected]
Phone:
+1 317 903 5640