Findings from CAROLINA trial show Tradjenta did not increase CV risk in patients with type 2 diabetes

Boehringer Ingelheim and Eli Lilly and Company announced detailed findings from the CAROLINA trial demonstrating that Tradjenta (linagliptin) did not increase cardiovascular risk compared with glimepiride (Amaryl) in adults with type 2 diabetes and cardiovascular risk . 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 Tradjenta 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 Tradjenta group compared with 12.0% (362 people) of the glimepiride group. The overall safety profile of Tradjenta in CAROLINA was consistent with previous data, and no new safety signals were observed. The study assessed Tradjenta 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. Tradjenta was similar to glimepiride in the secondary endpoint of 3P-MACE plus hospitalization for unstable angina (4P-MACE) (13.2% for Tradjenta versus 13.3% for glimepiride).

In CAROLINA, a higher proportion of the Tradjenta group (16.0%) achieved the secondary composite efficacy endpoint of treatment sustainability compared with the glimepiride group (10.2%). Compared with glimepiride, Tradjenta demonstrated similar overall effects on A1C, but reduced the relative risk for hypoglycemia (low blood sugar) by 77% (10.6% of patients treated with Tradjenta experienced any hypoglycemic incident versus 37.7% for glimepiride). This risk reduction was consistent across all hypoglycemia categories, including severe hypoglycemia requiring hospitalization. Tradjenta was also associated with a modest weight reduction of 1.5 kg versus glimepiride.

About Boehringer + Eli Lilly cardiovascular outcome trials : Cardiovascular outcome trials are highly relevant, as cardiovascular disease is a major complication and the leading cause of death in people with 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 OUTCOME with 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 type 2 diabetes medicine approved by the FDA to reduce the risk of cardiovascular death. CAROLINA is one of two cardiovascular outcome trials with the DPP-4 inhibitor Tradjenta. CAROLINA and CARMELINA (CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in patients with type 2 diabetes at high vascular risk) provide one of the most comprehensive datasets on the long-term safety of a DPP-4-inhibitor across a broad range of patients with type 2 diabetes. CARMELINA is a multi-national, randomized, 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 Tradjenta on cardiovascular and kidney safety in adults with type 2 diabetes at high risk for cardiovascular and/or kidney disease. The study met its primary endpoint, with Tradjenta demonstrating a similar cardiovascular safety profile compared with placebo when added to standard of care. CARMELINA also included a key secondary composite endpoint,showing a similar kidney safety profile compared with placebo. The overall safety profile of Tradjenta in CARMELINA was consistent with previous data, and no new safety signals were observed. CARMELINA also showed a similar rate of hospitalization for heart failure for Tradjenta compared with placebo.