Abstract Body (Do not enter title and authors here): Background
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat type 2 diabetes mellitus, but they have also shown benefits in mitigating cardiovascular risk. Given the increasing evidence of their efficacy in diverse disease states and their proposed mechanisms of action, it is plausible that SGLT2i could improve outcomes in patients with acute myocardial infarction (AMI) if administered early after presentation. However, the efficacy and safety of these therapies when used early in the course of acute coronary heart disease remain largely unexplored.

Objective
The aim of this current study was to assess the benefit of early initiation of SGLT2i after AMI.

Methods
We searched the Cochrane Central Registry of Controlled Trials, PubMed, Embase, Web of Science, and clinicalTrials.gov databases for all randomized controlled trials (RCTs) published up to May 2024 comparing SGLT2 inhibitors to placebo. The primary clinical endpoints included overall mortality, cardiovascular (CV) death, heart failure (HF) hospitalization, and adverse effects. Data were analyzed using a random-effects model to account for potential heterogeneity among the included studies. Significant heterogeneity was defined as an I-squared statistic ≥ 50%; a fixed-effects model was employed if heterogeneity was not significant. The odds ratio (OR) with a 95% confidence interval (CI) was calculated for each endpoint.

Results
Four RCTs were included in the analysis, comprising 11,108 patients (SGLT2i, n = 5,561; placebo, n = 5,547) who enrolled with a mean age of 63±9 years and 77% males. SGLT2i were associated with a 28% reduction in risk of HF hospitalization (OR: 0.72 [95% CI, 0.59-0.88]; p = 0.001; I² = 0%). However, there was no significant reduction in overall mortality (OR: 1.01 [95% CI, 0.83-1.23]; p = 0.93; I² = 27%), CV mortality (OR: 1.04 [95% CI, 0.83-1.30]; p = 0.74; I² = 0%), and serious adverse effects (OR: 1.06 [95% CI, 0.87-1.28]; p = 0.59; I² = 62%).

Conclusion
In patients with AMI, early initiation of SGLT2i was associated with a lower risk of HF hospitalization without increasing the incidence of serious adverse effects when compared to placebo. However, no significant difference was observed in overall mortality and CV deaths.