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

Area of Science:

• Cardiology
• Pulmonology
• Pharmacology

Background:

• The cardiovascular and respiratory safety profiles of sodium-glucose cotransporter 2 (SGLT2) inhibitors at varying doses require further elucidation.
• Serious adverse events (SAE) associated with SGLT2 inhibitors encompass a broad spectrum of cardiopulmonary conditions.

Purpose of the Study:

• To conduct a meta-analysis investigating the association between high-dose and low-dose SGLT2 inhibitors and specific cardiovascular and respiratory SAEs.
• To synthesize risk ratios (RR) and 95% confidence intervals (CI) for these associations, stratified by SGLT2 inhibitor dosage.

Main Methods:

• Inclusion of data from 9 large cardiorenal outcome trials of SGLT2 inhibitors.
• Meta-analysis performed on 86 types of cardiovascular SAE and 58 types of respiratory SAE.
• Stratification of analysis by SGLT2 inhibitor dose (high vs. low) compared to placebo.

Main Results:

• SGLT2 inhibitors (high or low dose) were associated with decreased risks for 6 cardiovascular SAEs, including bradycardia (RR, 0.60; 95% CI, 0.41-0.89) and atrial fibrillation (RR, 0.79; 95% CI, 0.69-0.92).
• A reduced risk was also observed for 6 respiratory SAEs, such as asthma (RR, 0.59; 95% CI, 0.37-0.93) and chronic obstructive pulmonary disease (RR, 0.77; 95% CI, 0.62-0.96).
• No significant associations were found for 132 other cardiopulmonary SAEs, and subgroup analysis by dose showed no significant differences (P > 0.05).

Conclusions:

• High- and low-dose SGLT2 inhibitors are associated with a reduced risk of 12 specific cardiopulmonary disorders.
• These findings suggest a potential therapeutic role for SGLT2 inhibitors in the prevention and treatment of bradycardia, atrial fibrillation, hypertensive emergencies, asthma, COPD, and sleep apnea syndrome.