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Assessment of Cardiovascular Risk With Glucagon-Like Peptide 1 Receptor Agonists in Patients With Type 2 Diabetes Using an Alternative Measure to the Hazard Ratio.

The Annals of pharmacotherapy
July 1, 2018
Masayuki Kaneko et al. (2 authors)
Journal ArticleRandomized Controlled TrialHuman Study
Extracted Claims (8)
InterventionDirectionEndpointPopulationDosageImpactClaim #
lixisenatide
no change
primary composite endpoint of cardiovascular events
patients in ELIXA trial
0 days [-14, 14]
difference of RMSTs for primary composite endpoint of cardiovascular events
#1
liraglutide
increase
primary composite endpoint of cardiovascular events
patients in LEADER trial
20 days [6, 34]
difference of RMSTs for primary composite endpoint of cardiovascular events
#2
semaglutide
increase
primary composite endpoint of cardiovascular events
patients in SUSTAIN-6 trial
8 days [1, 15]
difference of RMSTs for primary composite endpoint of cardiovascular events
#3
exenatide
no change
primary composite endpoint of cardiovascular events
patients in EXSCEL trial
11 days [-3, 26]
difference of RMSTs for primary composite endpoint of cardiovascular events
#4
GLP-1 receptor agonists
no change
risk of other cardiovascular outcomes
-
no substantial differences
no substantial differences for risk of other cardiovascular outcomes
#5
liraglutide
decrease
risk of major adverse cardiovascular events
-
-
decrease the risk of major adverse cardiovascular events
#6
semaglutide
decrease
risk of major adverse cardiovascular events
-
-
decrease the risk of major adverse cardiovascular events
#7
GLP-1 receptor agonists
no change
risk of cardiovascular outcomes
-
-
do not increase the risk of cardiovascular outcomes
#8
Abstract

BACKGROUND: Randomized clinical trials with the aim of evaluating the cardiovascular risks associated with glucagon-like peptide 1 (GLP-1) receptor agonists, lixisenatide, liraglutide, semaglutide, and exenatide, have been conducted. They showed different results among the agents, but the reason has not been explained. OBJECTIVE: To evaluate the cardiovascular risks associated with GLP-1 receptor agonists by using an alternative measure to the hazard ratio. METHODS: We used the difference in restricted mean survival time (RMST) as a measure of cardiovascular risks. Four randomized clinical trials with cardiovascular events as a primary endpoint, ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide), were reevaluated by estimating the RMSTs for each of the agents and placebo based on the reconstructed individual patient data for each time-to-event outcome from publicly available information. RESULTS: The differences of RMSTs (GLP-1 receptor agonist minus placebo: point estimate and 95% CI) for primary composite endpoint of cardiovascular events were 0 days [-14, 14] in ELIXA (1080 days follow-up), 20 days [6, 34] in LEADER (1620 days follow-up), 8 days [1, 15] in SUSTAIN-6 (672 days follow-up), and 11 days [-3, 26] in EXSCEL (1825 days follow-up). As for the risk of other cardiovascular outcomes, there were no substantial differences between GLP-1 receptor agonists and placebo. CONCLUSIONS: Liraglutide and semaglutide decrease the risk of major adverse cardiovascular events compared with placebo when using the difference in RMST. The previously reported result that GLP-1 receptor agonists do not increase the risk of cardiovascular outcomes compared with placebo is also confirmed.

Medical Subject Headings (MeSH)
Cardiovascular DiseasesDiabetes Mellitus, Type 2ExenatideFemaleGlucagon-Like PeptidesHumansHypoglycemic AgentsLiraglutideMaleMiddle AgedPeptidesProportional Hazards ModelsRisk FactorsGlucagon-Like Peptide-1 Receptor Agonists
Study Links
PubMed ID29424239
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Assessment of Cardiovascular Risk With Glucagon-Like Peptide... | Panacea Index