Cardiovascular Effects of Liraglutide

Background: Liraglutide is a glucagon-like 1 (GLP-1) agonist approved for treatment of type 2 diabetes and obesity. Objective: To review the cardiovascular effects of liraglutide including macrovascular and microvascular events, its use in heart failure, and its effects on heart rate and blood pressure. Results: The impact of liraglutide on cardiovascular outcomes was examined in a large welldesigned study published in 2016, the LEADER trial. This study included 9,340 patients with advanced type 2 diabetes and high baseline cardiovascular risk. The primary outcome was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 3.8 years, patients randomized to liraglutide had significant reduction in the composite primary outcome compared to patients randomized to placebo, hazard ratio (HR) 0.87; 95% CI 0.78-0.97. Death from cardiovascular causes was significantly reduced with liraglutide therapy (HR, 0.78; 95% CI 0.66-0.93), as well as death from any cause (HR, 0.85; 95% CI 0.74-0.97). In 2017, the LEADER investigators reported that nephropathy events were significantly lower after liraglutide therapy than placebo (HR 0.78; 95% CI 0.67-0.92), but there was no significant difference in retinopathy events. Meanwhile, other studies suggested that the use of liraglutide may be harmful in patients with severe heart failure, in part due to increase in heart rate. Conclusion: Liraglutide is a useful therapy in patients with advanced type 2 diabetes complicated by cardiovascular disease, except patients with severe heart failure. Further studies are needed to evaluate the long-term effects of liraglutide, and to see whether its beneficial effects extend to patients with type 2 diabetes and low cardiac risk.