Efficacy and Safety of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Ventricular Arrhythmias and Cardiovascular Events: A Disease-Stratified Network Meta-Analysis.

In 30 seconds

This disease-stratified network meta-analysis compared SGLT2 inhibitors and GLP-1 receptor agonists for ventricular arrhythmias and cardiovascular outcomes in people with type 2 diabetes, heart failure, or both. It included 32 independent randomised controlled trials involving 140 156 participants. Most agents did not significantly increase ventricular arrhythmia risk; empagliflozin had an exploratory association with lower risk in the type 2 diabetes network (OR 0.31, 95% CI 0.11-0.86). SGLT2 inhibitors consistently reduced hospitalisation for heart failure across both networks, while mortality benefits were reported for selected agents in specified populations.

Key findings

• Empagliflozin showed an exploratory signal for lower ventricular arrhythmia risk in the type 2 diabetes network (OR 0.31, 95% CI 0.11-0.86).
• SGLT2 inhibitors consistently reduced hospitalisation for heart failure across the heart failure and type 2 diabetes networks.
• Dapagliflozin in the heart failure network, and empagliflozin and liraglutide in the type 2 diabetes network, were associated with lower cardiovascular and all-cause mortality.

Why it matters

The analysis addresses whether these widely used drug classes affect ventricular arrhythmias alongside major cardiovascular outcomes. Its findings are broadly reassuring about arrhythmia risk and reinforce the heart-failure hospitalisation benefit associated with SGLT2 inhibitors. However, indirect comparisons and exploratory signals should not be treated as proof that one agent is superior to another.

What to keep in mind

Evidence networks were largely placebo-centred and lacked closed loops, making between-drug comparisons dependent on the transitivity assumption. Safety outcomes were limited by sparse events and non-uniform adverse-event reporting.