Clinical knowns and mechanistic unknowns: cardioprotection and inflammation modulation of GLP-1 receptor agonists and SGLT2 inhibitors

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. In the recent years, clinical trials of sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonist (GLP-1RAs) have demonstrated positive results for several cardiovascular end points. In addition to the positive clinical end point-focused trials, several mechanistic and clinical studies have outlined inflammation-modulating properties of SGLT2 inhibitors and GLP-1RAs. However, limited data exist on precise ways in which these therapies alter immune responses, which in turn play a central role in linking metabolic changes to inflammation regulation and ultimately end organ activities. This review summarizes the known and putative immune/inflammatory-modulating effects of SGLT2 inhibitors and GLP-1RAs, as well as the evidence for cardiovascular benefit from outcomes trials that are currently available.