15 February 2019 - - German pharmaceutical company Boehringer Ingelheim and US-based Eli Lilly and Company's (NYSE: LLY) 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), the companies said.

CAROLINA is the only active-comparator cardiovascular outcome trial for a dipeptidyl peptidase-4 (DPP-4) inhibitor.

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.

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 six years.

The overall safety profile of linagliptin in CAROLINA was consistent with previous data and no new safety signals were observed.

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.

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, CAROLINA confirms linagliptin's long-term overall safety profile in a broad range of adults with type 2 diabetes.

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

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 six years.

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).

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.

These people reflect patients that doctors typically see in their daily clinical practice.

CAROLINA was led by an academic trial steering committee and Boehringer Ingelheim and Eli Lilly and company. CAROLINAis the first DPP-4 inhibitor, active-comparator cardiovascular outcome trial.

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, liver and kidney function.

Trajenta has the lowest kidney excretion rate of all DPP-4 inhibitors.

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.

In 2015, Boehringer Ingelheim and Eli Lilly and company announced results from the landmark cardiovascular outcome trial EMPA-REG OUTCOMEwith the SGLT2 inhibitor empagliflozin, which reduced the relative risk of cardiovascular death by 38% in adults with type 2 diabetes and established cardiovascular disease, on top of standard of care.

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.

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) 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.

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.

The trial met its primary endpoint,17 with linagliptin demonstrating a similar cardiovascular safety profile compared to placebo when added to standard of care.

CARMELINA also included a key secondary composite endpoint, showing a similar kidney safety profile compared to placebo. The overall safety profile of linagliptin in CARMELINA was consistent with previous data and no new safety signals were observed.

CARMELINA also showed a similar rate of hospitalisation for heart failure for linagliptin compared to placebo.