Therapy Areas: Diabetes
Full Data from CAROLINA Outcome Trial Support Long-Term Cardiovascular Safety Profile of Trajenta
12 June 2019 - - German pharmaceutical company Boehringer Ingelheim and US-based Eli Lilly and Company (NYSE: LLY) have released 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, the company said.
The findings were reported 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% (356 people) of the linagliptin group compared to 12% (362 people) of the glimepiride group.
The overall safety profile of linagliptin in CAROLINA was consistent with previous data, and no new safety signals were observed.
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 six years.
Linagliptin was similar to glimepiride in the secondary endpoint of 3P-MACE plus hospitalisation for unstable angina (4P-MACE - 13.2% for linagliptin versus 13.3% for glimepiride).
In CAROLINA, a higher proportion of patients within the linagliptin group (16.0 %) achieved the secondary composite efficacy endpoint of treatment sustainability versus the glimepiride group (10.2%).
Compared with glimepiride, linagliptin demonstrated similar overall effects on HbA1c, but significantly reduced the relative risk for hypoglycaemia (low blood sugar) by 77% (10.6% of patients treated with linagliptin experienced any hypoglycaemic incident versus 37.7% for glimepiride).
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.
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 only 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.2 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.
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.
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, 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.2,14 CARMELINA also showed a similar rate of hospitalisation for heart failure for linagliptin compared to placebo.


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