Physicians' Academy for Cardiovascular Education

No improvement of systolic function with GLP-1 analogue in chronic HF patients with diabetes

Literature - Jorsal A, et al, Eur J Heart Fail, 2016

Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial


Jorsal A, Kistorp C, Holmager P, et al.
Eur J Heart Fail 2016; published online ahead of print
 

Background

In heart failure (HF) patients with reduced left-ventricular ejection fraction (LVEF), ACE-inhibitors, beta-blockers, and spironolactone reduce mortality and improve LVEF, but long-term survival and quality of life remain impaired, especially in patients with diabetes [1,2]. Glucagon-like peptide-1 (GLP-1) stimulates insulin production, inhibits glucagon excretion, reduces blood glucose, and some data suggest that it positively contributes to left-ventricular (LV) function, although there are no long-term confirmation data [3,4].
 
In this randomized study, the effects of 24-week treatment with the GLP-1 analogue liraglutide (1.8 mg subcutaneous injection once a day) versus placebo on LV function in 241 stable chronic HF patients with reduced LVEF with and without type 2 diabetes mellitus (T2DM) was investigated.
 

Main results

  • The mean absolute increase in LVEF was 0.7±5.4% in the liraglutide group and 1.5±5.0% in the placebo group (mean difference −0.8%, 95% CI: −2.1 to 0.5, P=0.24). 
  • The multiple linear regression analysis of the relation between the LVEF change and treatment, adjusted for age, T2DM, BMI, LVEF, ischaemic heart disease, and eGFR, did not change the overall conclusion.
  • There was no interaction with T2DM status for the LVEF change (P=0.59).
  • The atrial volume decreased significantly in the liraglutide group compared with the placebo group (mean difference −8.7 mL, 95% CI: −14.2 to −3.2, P=0.002).
  • At the end of the study, patients in the liraglutide group were able to walk 28±65 meters longer in the 6-minute walk test compared with 3±89 meters in the placebo group (mean difference 24 meters, 95% CI: 2-47, P=0.04).
  • Liraglutide treatment was associated with a weight loss of 2.2±3.1 kg. There was no change in the placebo group (0.0±3.0 kg).
  • Although systolic blood pressure (SBP) was reduced in the liraglutide group, there was no statistically significant difference between the treatment groups.
  • There was an increase in heart rate of on average 6±9 bpm in the liraglutide group and an average decrease of 1±8 bpm in the placebo group (mean difference 7 bpm, 95% CI: 5-9, P<0.0001).  
  • After 24 weeks of treatment, HbA1c was reduced in the liraglutide group compared with the placebo group (mean difference −0.4%, 95% CI: −0.5 to −0.3, P<0.0001).
  • More patients experienced serious cardiac adverse events in the liraglutide group compared with the placebo group (10% vs. 3% resp., P=0.04). The events were one death caused by ventricular tachycardia (VT), non-fatal VT, atrial fibrillation requiring intervention, worsening of ischaemic heart disease, and one case of worsening HF.
 

Conclusion

In patients with stable chronic HF and reduced LVEF and T2DM, no difference with regard to changes in LVEF or other systolic function measures were observed between the liraglutide and the placebo group. On the other hand, liraglutide was associated with an substantial increased heart rate and more serious adverse events compared with placebo.
 
Find this article online at Eur J Heart Fail.
 

References

1. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293–302.
2. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–2007.
3. Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res 2014;114:1788–1803.
4. Chen WR, Hu SY, Chen YD, et al. Effects of liraglutide on left ventricular function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am Heart J 2015;170:845–854.