Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a new antihyperglycemic
class with the demonstrated advantage of reducing major adverse cardiovascular events
(MACE) among individuals with type 2 diabetes (T2DM), atherosclerotic cardiovascular disease, or high cardiovascular
Objective: Τo summarize the evidence of systematic reviews (SRs) that assess MACE (cardiovascular mortality,
nonfatal myocardial infarction, and stroke) and hospitalizations for heart failure in GLP-1RAs-treated patients
and to evaluate possible overlap in pertinent SRs.
Methods: We performed a comprehensive search via MEDLINE, Cochrane Library, and PROSPERO databases
up to February 23, 2020, for SRs examining cardiovascular outcomes of GLP-1RAs in T2DM patients. Three
independent authors extracted data and assessed the methodological quality of the included SRs using the
Results: We found 37 SRs – published between 2009 and 2020 in English – of which 35 collected data only
from randomized clinical trials while two from observational studies as well. The methodological quality of the
37 SRs ranged from low to high, while only 3 have evaluated the overall quality of evidence outcome using the
Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. All the included
SRs showed cardiovascular safety of GLP-1RAs while the latest ones demonstrated a reduction in composite
MACE endpoint as well as its every individual component and heart failure hospitalizations.
Conclusion: In the first overview of SRs about cardiovascular outcomes of GLP-1RAs, they proved favorable
effects on reducing cardiovascular events in T2DM patients. There are, however, many overlapping reviews
based on relatively few cardiovascular outcomes trials.