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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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)