Memorandum
Results from the FIGHT trial, recently published in JAMA demonstrate that GLP-1 agonist liraglutide (Novo Nordisk’s Victoza) does not improve clinical stability in patients recently-hospitalized for acute heart failure. The randomized placebo-controlled trial (n=300 patients with and without type 2 diabetes) found no significant difference between the liraglutide-treated group and the placebo group in primary composite endpoint (time to death, time to re-hospitalization for heart failure, and time-averaged proportional change in BNP) Furthermore, there was no significant difference in cardiovascular (CV) deaths (12% vs. 11% respectively, p=0.78) or in re-hospitalizations (41% vs. 34% respectively, p=0.17) between the two groups. This trend held true in the subgroup analysis of type 2 diabetes patients (n=178), where type 2 patients in the liraglutide group showed no significant difference from patients in the placebo group for the primary endpoint. Previously, in the LEADER trial, the effect of liraglutide on hospitalization for heart failure in people with type 2 diabetes at high cardiovascular risk trended in a positive direction but didn’t reach statistical significance (hazard ratio 0.87, p=0.14); no such positive trend was observed in the FIGHT trial. These findings are not altogether surprising given that the finding of cardioprotective benefit in the LEADER trial was driven by a reduction in atherosclerotic endpoints of MI, stroke, and cardiovascular death and liraglutide improves long-term risk factors such as obesity and inflammation. Furthermore, the LEADER trial examined a very different patient population from the FIGHT trial – while many of the patients in LEADER were at high or very high risk for cardiovascular events, few had been recently hospitalized for heart failure. In contrast, every patient in FIGHT was recently-hospitalized for heart failure. As a result, FIGHT examined the potential of liraglutide as a tertiary prevention method while LEADER examined primary or secondary prevention. We’d be very interested in seeing the results from a similar trial of Lilly/BI’s Jardiance (empagliflozin), given the acute effect empagliflozin demonstrated on hospitalization for heart failure in the EMPA-REG OUTCOME trial, and hope that Lilly/BI’s planned studies of Jardiance in heart failure patients with and without diabetes may be able to shed light on this point.
-- by Payal Marathe, Helen Gao, and Kelly Close