Lynchburg Journal of Medical Science

Lynchburg Journal of Medical Science


Family Medicine


Dr. Thomas Colletti, DHSc, MPAS, PA-C


Purpose: This article reviews the cardiovascular benefits and reduction in Major Adverse Cardiovascular Events (MACE) and secondary cardiovascular risk reduction associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP1-RA). This article focuses on the treatment of type 2 diabetes mellitus, both with and without known cardiovascular disease.

Method: A literature review of the studies acquired through the PubMed database on SGLT-2i: canagliflozin, dapagliflozin, and empagliflozin; as well as GLP1-RA: exenatide, dulaglutide, and semaglutide was conducted. Cardiovascular Outcome Trials (CVOT) for each of the six drugs were accepted for evaluation in this literature review. Comparison of the primary outcomes for MACE (composite of total death: myocardial infarction [MI], cerebrovascular accident [CVA], and hospitalization due to heart failure [HF]) and secondary clinical endpoints were reviewed.

Results: The cardiovascular benefit and reduction of MACE were evaluated in this in-depth head-to-head CVOT comparison of the leading SGLT-2i and GLP1-RA medications. A secondary comparison for reducing cardiovascular risk was also completed. A comparison of the three SGLT-2i medications revealed both primary MACE reduction or prevention, as well as weight loss, glycated hemoglobin improvement, and improved blood pressure control. Canagliflozin produced the most significant reduction in glycated hemoglobin levels in this class, while empagliflozin produced the most substantial reductions in primary MACE. There was a class effect reduction in hospitalizations due to heart failure for SGLT-2 inhibitors. Primary MACE reduction, as well as weight and glycated hemoglobin levels, were significantly reduced in the GLP1-RA class. Semaglutide produced the greatest reductions across all major endpoints. A reduction in stroke was found to be a class effect for the GLP1-RA medications.

Conclusion: Type 2 diabetes mellitus (T2DM) is commonly treated with SGLT-2i and GLP1-RA drug classes. Many of the medications in these classes have been shown to have statistical significance in lowering MACE. Both SGLT-2i and GLP1-RA medications help with weight loss, systolic and diastolic blood pressure control, and glycated hemoglobin levels (HgbA1c). In comparing these CVOTs, GLP1-RA has a greater potential for reducing both primary MACE outcomes and nonfatal CVAs. However, the SGLT-2i class should be considered in renal and heart failure patients. Empagliflozin produced the greatest reduction in heart failure hospitalizations, whereas semaglutide had the most significant reduction in nonfatal strokes.


Available when accessing via a campus IP address or logged in with a University of Lynchburg email address.

Off-campus users can also use 'Off-campus Download' button above for access.