Are High- or Low-dose SGLT2 Inhibitors Associated With Cardiovascular and Respiratory Adverse Events? A Meta-analysis

Abstract: The association between high-dose or low-dose sodium-glucose cotransporter 2 (SGLT2) inhibitors and various cardiovascular and respiratory serious adverse events (SAE) is unclear. Our meta-analysis aimed to define the association between high-dose or low-dose SGLT2 inhibitors and 86 kinds of cardiovascular SAE and 58 kinds of respiratory SAE. We included large cardiorenal outcome trials of SGLT2 inhibitors. Meta-analysis was conducted and stratified by the dose of SGLT2 inhibitors (high dose or low dose) to synthesize risk ratio (RR) and 95% confidence interval (CI). We included 9 trials. Compared with placebo, SGLT2 inhibitors used at high dose or low dose were associated with the decreased risks of 6 kinds of cardiovascular SAE [eg, bradycardia (RR, 0.60; 95% CI, 0.41–0.89), atrial fibrillation (RR, 0.79; 95% CI, 0.69–0.92), and hypertensive emergency (RR, 0.34; 95% CI, 0.15–0.78)] and 6 kinds of respiratory SAE [eg, asthma (RR, 0.59; 95% CI, 0.37–0.93), chronic obstructive pulmonary disease (RR 0.77, 95% CI 0.62–0.96), and sleep apnea syndrome (RR 0.37, 95% CI 0.17–0.81)]. SGLT2 inhibitors used at high dose or low dose did not show significant associations with 132 other cardiopulmonary SAE. For any outcome of interest, the subgroup difference according to the dose of SGLT2 inhibitors was not significant ( P subgroup > 0.05). SGLT2 inhibitors used at whether high dose or low dose are associated with the decreased risks of 12 cardiopulmonary disorders (eg, bradycardia, atrial fibrillation, hypertensive emergency, asthma, chronic obstructive pulmonary disease, and sleep apnea syndrome). These findings may suggest the potential efficacy of high- or low-dose SGLT2 inhibitors for the prevention and treatment of these cardiopulmonary disorders.