Abstract Body (Do not enter title and authors here): Background: Historically, patients with type 2 diabetes mellitus (T2DM) and concurrent cardiovascular disease (CVD) have been managed through multifactorial interventions, including lifestyle modifications. Recently, empagliflozin, a potent sodium-glucose cotransporter 2 inhibitor (SGLT2i), has emerged as a novel antidiabetic agent demonstrating significant improvements in cardiovascular outcomes.

Aim: To conduct a meta-analysis comparing empagliflozin with placebo in patients with T2DM and concomitant CVD.

Methods: We performed a thorough literature search of PubMed, EMBASE, and the Cochrane Library up to May 2024 to identify studies comparing empagliflozin with placebo in patients with T2DM and concomitant CVD. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes and standard mean difference (SMD) or mean differences (MD) for continuous outcomes, each accompanied by 95% confidence intervals (CIs). Due to varying units of measurement for HbA1c that were not interconvertible, SMD was employed. Conversely, MD was used for the analysis of other continuous outcomes.

Results: 16 studies fulfilled the inclusion criteria. Empagliflozin significantly reduced HbA1c (SMD: -1.33 [-2.28, -0.38]; p=0.006; Figure) and cardiac mortality (RR= 0.62 [0.50, 0.78]; p<0.0001), in comparison to placebo. Empagliflozin was also associated with a significantly greater reduction in systolic blood pressure (MD: -5.22 [-7.97, -2.47]; p=0.0002) and diastolic blood pressure (MD: -3.31 [-5.76, -0.85]; p= 0.008). However, empagliflozin was associated with a significantly greater risk of genital infections (RR=3.66 [2.69, 5.00]; p<0.00001).

Conclusion: In individuals diagnosed with T2DM and CVD, the use of empagliflozin could lead to improved clinical results.