The cardio-renal-metabolic role of the nod-like receptor protein-3 and senescence-associated secretory phenotype in early sodium/glucose cotransporter-2 inhibitor therapy in people with diabetes who have had a myocardial infarction.

Aims: Following an acute myocardial infarction (AMI), individuals with type 2 diabetes (T2DM) have a 2-to-3 fold increased risk of mortality compared to those without diabetes, and globally cardiorenal complications account for 50% of diabetes-related deaths. The use of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in people with T2DM-AMI is associated with decreased inflammatory burden and improved cardiorenal outcomes. The mechanisms behind this protection are unclear and form the basis of this study.

Methods: This single centre, prospective study with randomisation will utilise plasma and monocyte-derived macrophages from patients with T2DM who have recently had an AMI and are prescribed Empagliflozin (SGLT2i) either immediately following the acute cardiac event or at 3 months post-AMI.

Results: The study will test the hypothesis that Empagliflozin provides anti-inflammatory protection by suppressing systemic NOD-like receptor protein-3 (NLRP3) inflammasome activation and the pro-inflammatory senescence-associated secretory phenotype (SASP), perpetrators of sterile (non-pathogen evoked) inflammation linked to poor clinical outcomes in T2DM-AMI patients. The study will also assess the benefits of early intervention on these parameters.

Conclusions: Elucidating a role for an SGLT2i in suppressing sterile inflammation will enhance understanding of how they can be used effectively to treat cardiorenal complications and will identify novel pathways for future intervention. Furthermore, the optimal timing of when to initiate SGLT2i therapy post-AMI is unclear. Correlating the level of protection to the onset of therapy in individuals with T2DM, AMI and at cardiovascular risk will establish if Empagliflozin provides greater benefit when intervention is initiated earlier.