Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus

Abstract

Background: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose contransporter-2 inhibitors (SGLT2i) have emerged as two new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease (ASCVD) for different outcomes with these classes of drugs remain undefined. Methods: We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases. The primary outcomes were: the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and progression of kidney disease. Results: In total, data from 8 trials and 77,242 patients, 42,920 (55.6%) in GLP1-RA trials and 34,322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1RA reducing the risk by 12% (HR 0.88, 95%-CI 0.84 to 0.94; pConclusions: In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established ASCVD, whereas SGLT2i have a more marked effect on preventing HHF and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with T2DM.