• Trajenta^®      demonstrates no increased cardiovascular risk compared to glimepiride in      adults with type 2 diabetes and cardiovascular risk

• With a median follow-up of      more than 6 years, CAROLINA^® adds evidence to the long-term      safety profile of Trajenta^® in a broad range of adults with      type 2 diabetes

INGELHEIM, Germany & INDIANAPOLIS -- (BUSINESS WIRE) --

Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced CAROLINA^® (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) met its primary endpoint, defined as non-inferiority of Trajenta^® (linagliptin) vs glimepiride in time to first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (3P-MACE).^1,2

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CAROLINA^® is the only active-comparator cardiovascular outcome trial for a dipeptidyl peptidase-4 (DPP-4) inhibitor.^1,2 The trial evaluated the cardiovascular safety of linagliptin (5 mg once daily) compared to the sulphonylurea glimepiride, on top of standard of care in 6,033 adults with type 2 diabetes and increased cardiovascular risk or established cardiovascular disease.^1,2 The trial 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.^1,2 The overall safety profile of linagliptin in CAROLINA^® was consistent with previous data and no new safety signals were observed.³

People who have type 2 diabetes are at an increased risk of cardiovascular disease and, despite recent advancements in treatment options, cardiovascular disease remains the leading cause of death for this population.⁴ Together with CARMELINA^®, the placebo-controlled cardiovascular outcome trial, which demonstrated long-term cardiovascular safety in adults with type 2 diabetes at high risk for heart and kidney disease,⁵ CAROLINA^® confirms linagliptin’s long-term overall safety profile in a broad range of adults with type 2 diabetes.

“Many guidelines recommend early use of a diabetes treatment with cardiovascular benefit,” said Waheed Jamal, MD, Corporate Vice President and Head of Cardiovascular & Metabolic Medicine, Boehringer Ingelheim. “When other therapies such as DPP-4 inhibitors are considered for people with type 2 diabetes, physicians need a treatment with an established long-term safety profile. With these results, CAROLINA^® expands our understanding of the long-term cardiovascular safety of linagliptin, which now has one of the most comprehensive datasets on the cardiovascular safety of a DPP-4 inhibitor.”

“These data provide further confidence in the well-established safety and tolerability profile of linagliptin for the treatment of adults with type 2 diabetes,” added Jeff Emmick, MD, PhD, Vice President, Product Development, Lilly Diabetes. “Linagliptin is an important option for physicians considering a DPP-4 inhibitor for their patients with type 2 diabetes. Boehringer Ingelheim and Lilly look forward to sharing the full results later this year.”

The full results of CAROLINA^® will be presented on 10 June at the American Diabetes Association’s 79^th Scientific Sessions in San Francisco, United States.

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.^1,2 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).² 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.^1,2 These people reflect patients that doctors typically see in their daily clinical practice.⁶

CAROLINA^® was led by an academic trial steering committee and Boehringer Ingelheim and Eli Lilly and Company. CAROLINA^® is the first 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.³ Trajenta^® has the lowest kidney excretion rate of all DPP-4 inhibitors.^7,8,9,10

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.⁴ 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.^{11,12,13,14,15} 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.^1,2 CAROLINA^® and the CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in patients with type 2 diabetes at high vascular risk trial (CARMELINA^®)^5,16 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.^5,14 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.^5,14 The trial met its primary endpoint,¹⁷ with linagliptin demonstrating a similar cardiovascular safety profile compared to placebo when added to standard of care.⁵ CARMELINA^® also included a key secondary composite endpoint,¹⁸ showing a similar kidney safety profile compared to placebo.⁵ The overall safety profile of linagliptin in CARMELINA^® was consistent with previous data and no new safety signals were observed.^3,5 CARMELINA^® also showed a similar rate of hospitalisation for heart failure for linagliptin compared to placebo.⁵