Study data published Thursday in the NEJM showed that Eli Lilly and Boehringer Ingelheim's Jardiance (empagliflozin) significantly reduced the risk of the combined endpoint of cardiovascular (CV) death, non-fatal heart attack or non-fatal stroke, compared to placebo, when added to standard of care in patients with type 2 diabetes at high risk of CV events. Results from the study, which were presented at the European Association for the Study of Diabetes (EASD) annual meeting, also revealed that the SGLT-2 inhibitor was associated with lower risks of all-cause mortality and hospitalisation for heart failure. Shares in Eli Lilly gained as much as 6.3 percent on the news.
In the EMPA-REG OUTCOME trial, for which top-line results were announced last month, 7020 patients with type 2 diabetes at high risk of CV complications were randomised to one of two once-daily doses of Jardiance or placebo, both in combination with standard of care. The primary composite outcome was death from CV causes, non-fatal myocardial infarction, or non-fatal stroke, while the key secondary composite endpoint was the primary outcome plus hospitalisation for unstable angina.
Results after a median follow-up of about three years illustrated that patients receiving Jardiance had a 14-percent lower rate of the primary composite outcome than did those in the placebo group. Specifically, the drug was associated with a significant 38-percent lower rate of death from CV causes, while no significant difference was noted in the risks of non-fatal heart attack or non-fatal stroke. Meanwhile, patients treated with Jardiance also had significantly reduced rates of heart failure hospitalisations and death from any cause, with relative risk reductions of 35 percent and 32 percent, respectively.
"Addressing the burden of cardiovascular events, including death, is at the core of diabetes care, and until now no single diabetes medication has been associated with a reduction in mortality," explained lead investigator Bernard Zinman. He described the results as "a very significant advance, something that people have been waiting for," adding that "we've had negative trials one after another that have been called neutral, so this is a long time in coming." Meanwhile, Leerink analyst Seamus Fernandez has suggested that a reduction in CV risk of 15 percent or more could prompt a revision in clinical guidelines.
Commenting on the news, Cleveland Clinic cardiologist Steven Nissen remarked "there are very few therapies we have in cardiovascular medicine that have ever shown a one-third reduction in the risk of cardiovascular death." Nissen noted that since CV disease is the leading cause of death in patients with diabetes, decreasing the rate of CV death "by 38 percent is a landmark result."
The EMPA-REG OUTCOME trial was conducted to meet regulatory demands that makers of diabetes drugs show their products do not increase CV risk. In 2013, research findings demonstrated that DPP-4 inhibitors did not increase the risk of myocardial infarction, but data from two CV outcomes trials suggested the drug class might be linked to a higher risk of hospitalisation due to heart failure. Earlier this year, Merck & Co. unveiled data from the TECOS outcomes study showing that its DPP-4 inhibitor Januvia (sitagliptin) did not elevate the risk of major adverse CV events, versus placebo.
For additional analysis, see ViewPoints: Full data bolster Jardiance’s clinical success, but commercial headway still in question.
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