On February 21, the FDA approved a new indication for Eli Lilly’s Trulicity (dulaglutide) to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. This approval makes Trulicity the only glucose-lowering medication indicated for both primary and secondary prevention to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes.
This approval was primarily based on data from the multicenter, randomized, double-blind, placebo-controlled REWIND study. The REWIND study enrolled 9,901 patients across 24 countries (baseline HbA1c of 7.3%, with 68.5% having no diagnosed cardiovascular disease) to primarily evaluate the impact of adding dulaglutide 1.5 mg (once weekly) versus placebo to standard care on major adverse cardiovascular events in patients with type 2 diabetes. The primary composite endpoint was the first occurrence of MACE (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Secondary endpoints included microvascular complications, hospitalization for angina, all-cause mortality, and hospitalization for heart failure. The follow-up period was 6.5 years.
The results showed that, compared with the placebo group, the dulaglutide treatment group had a 12% reduction in the risk of major adverse cardiovascular events (MACE) (HR 0.88, 95% CI 0.79–0.99, P=0.026), a significant 24% reduction in the risk of non-fatal stroke (HR 0.76, 95% CI: 0.62–0.94, P=0.017), a non-significant reduction in the risk of cardiovascular death (HR 0.91; 95% CI: 0.78–1.06, P=0.21), and a non-significant reduction in the risk of all-cause mortality (HR 0.90, 95% CI: 0.80–1.01). The treatment group also exhibited a 13% reduction in the risk of composite microvascular outcomes (HR 0.87, 95% CI: 0.79–0.95).
Hertzel Gerstein, lead investigator of the REWIND study and Deputy Director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences, stated: “The REWIND study evaluated, in a broad population more representative of real-world practice, whether dulaglutide could protect patients with type 2 diabetes from experiencing their first cardiovascular event and prevent further cardiovascular events in those with pre-existing cardiovascular disease. The finding that dulaglutide reduces the incidence of major adverse cardiovascular events (MACE) is striking. With approximately 415 million people living with type 2 diabetes worldwide, and diabetes itself being a risk factor for cardiovascular disease—one-third of patients with diabetes also have concurrent cardiovascular disease—the value of using Trulicity in diabetic patients without established cardiovascular disease is undoubtedly significant.”
Sherry Martin, Head of Medical Affairs at Eli Lilly, stated, “For the first time in diabetes clinical practice, healthcare providers can prescribe Trulicity to reduce the risk of cardiovascular events in patients with type 2 diabetes, regardless of whether they have pre-existing cardiovascular disease. With once-weekly injections, Trulicity not only helps patients achieve their glycemic control targets but also reduces cardiovascular risk, offering a remarkably simple treatment option.”
Trulicity is a long-acting GLP-1 receptor agonist and currently the best-selling GLP-1 class medication. Prior to dulaglutide, empagliflozin, liraglutide, canagliflozin, dapagliflozin, and semaglutide had successively been approved by regulatory authorities for reducing the risk of cardiovascular events in patients with type 2 diabetes; however, these approvals were specifically limited to patients with established cardiovascular disease. Dulaglutide is the first and only glucose-lowering agent approved to reduce the risk of cardiovascular events in patients with type 2 diabetes who do not have established cardiovascular disease. In 2019, global sales of Trulicity reached $4.128 billion.