GLP-1 receptor agonists reduce CV and all-cause mortality

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis

Literature - Bethel MA, Patel RA, Merrill P, et al. - Lancet Diab Endocrinol 2018;6:105–13

Introduction and methods

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering treatments for type 2 diabetes (T2DM). Findings in CV outcome trials demonstrated CV safety, but results for CV efficacy varied [1].

In this systematic review and meta-analysis, the CV efficacy and safety of GLP-1 receptor agonists were evaluated in the CV outcomes trials ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN (semaglutide), and EXSCEL (extended-release exenatide) [2-5]. These trials assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in 33,457 adult patients with T2DM aged ≥18 years.

The primary efficacy outcome for this meta-analysis was the effect of GLP-1 receptor agonists on the incidence of three-point MACE, including CV mortality, non-fatal myocardial infarction (MI), and non-fatal stroke, compared with placebo. The safety outcomes of interest were severe hypoglycemia, acute pancreatitis, pancreatic cancer, and medullary thyroid cancer.

Main results

The duration of follow-up ranged from 2.1 to 3.8 years.
The use of GLP-1 receptor agonists was associated with a significant 10% relative risk reduction (HR: 0.90; 95%CI: 0.82–0.99; P=0.033) of the primary endpoint, compared with placebo.
There was a significant relative risk reduction in CV mortality of 13% compared with placebo (HR: 0.87; 95%CI: 0.79–0.96; P=0.007), and a significant relative risk reduction in all-cause mortality of 12% (HR: 0.88; 95%CI: 0.81–0.95; P=0.002).
Compared with placebo, no significant effects of GLP-1 receptor agonists were seen for fatal and non-fatal MI, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure.
Compared with placebo, no significant effect of GLP-1 receptor agonists was seen on the proportions of patients who had severe hypoglycemia, acute pancreatitis, pancreatic cancer or medullary thyroid cancer.

Conclusion

A meta-analysis of available CV outcome studies with GLP-1 receptor agonists shows that they reduce MACE without significant safety concerns.

References

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Find this article online at Lancet Diab Endocrinol