Background: We thought to delve deeper into seven meta-analyses of major clinical trials
focusing on Glucagon-Like Peptide-One Receptor Agonist (GLP-1 RA) cardioprotective effect.
Aim: We explored the role of GLP-1 RA in cardiovascular risk protection as the primary outcome in
subjects with type 2 diabetes mellitus.
Methodology: The current review has explored and critically appraised seven meta-analyses of placebo-
controlled randomized clinical trials (RCT-s) involving GLP-1 RA used in diabetes that has exhibited
major cardiovascular events as the primary outcome.
Results: Based on the participants-intervention-comparison and outcomes (PICO), the total number of
the participants in this review were (138750), the intervention was conducted with GLP-1 RA, the
comparator was a placebo and the outcome was major cardiovascular events. The overall evidence for
the cardioprotective effect of GLP-1 RA in diabetes was very clear in subjects with the cardiovascular
risk of varying degrees. Most of the currently reviewed meta-analyses have not shown cardioprotection
with GLP-1 RA in subjects with diabetes exhibiting high cardiovascular risk or medical history
of cardiovascular diseases. Patient variability, in addition to potency parameters, will be the key to
a successful member of the class. There will be avenues for selection of a candidate based on the suitability
to patient preferences and characteristics.
Conclusion: The RCT-s for GLP-1 RA should characterize cardiovascular risk in subjects with diabetes
such that disparities between established cardiovascular risk (high, moderate and low) or medical
history of cardiovascular disease have been accounted for in subgroup analysis.