The FDA’s Endocrine and Metabolic Drug Advisory Committee is scheduled to vote next week on whether the diabetes medication empagliflozin (Jardiance, Eli Lilly/Boehringer Ingelheim) reduces the risk of cardiovascular death, according to documents posted online ahead of the June 28 meeting. The advisors will discuss whether the label for empagliflozin should include a claim that it cuts the risk of heart problems in patients at high risk.
Empagliflozin is a sodium-glucose cotransporter–2 (SGLT2) inhibitor approved by the FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus (T2DM). By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.
At the time of the drug’s approval, the FDA asked Lilly and Boehringer to conduct an additional clinical study of empagliflozin to show that the drug did not increase the risk of heart problems. In January 2016, the companies submitted results indicating that empagliflozin reduced the risk of death from heart attacks and strokes, becoming the first glucose-lowering medication to demonstrate protective effects in a large clinical trial. Now, the companies want to add those results to the drug’s label.
The EMPA-REG trial was a randomized, double-blind, placebo-controlled, parallel-group, event-driven study designed to compare the safety and efficacy of empagliflozin 10 mg once daily (n = 2,345) and empagliflozin 25 mg once daily (n = 2,342) with placebo (n = 2,333) as an add-on to standard- of-care treatment for diabetes and other cardiovascular risks in patients with T2DM. The primary endpoint was the time to first occurrence of an adjudicated major adverse cardiovascular event (MACE), defined as an incident event of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke (i.e., three-point MACE). The trial was to stop after 691 participants had experienced an adjudicated MACE event. The trial’s secondary endpoint was the time to first occurrence of adjudicated cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for unstable angina (i.e., four-point MACE).
The results demonstrated the noninferiority of empagliflozin compared with placebo in the number of cardiovascular outcomes, as measured by the primary three-point MACE and the secondary four-point MACE. Three-point MACE occurred in 10.4% and 10.6% of the patients treated with empagliflozin 10 mg once daily or 25 mg once daily, respectively, compared with 12.1% of the patients given placebo. Similarly, four-point MACE occurred in 12.8% of each of the empagliflozin groups compared with 14.3% of the placebo group.