Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in atherosclerotic cardiovascular disease phenotypes: a systematic review and meta-analysis

Background Atherosclerotic cardiovascular disease (ASCVD) encompasses various phenotypes with elevated risks of major adverse cardiovascular events (MACEs). This study aimed to assess the comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) across diverse ASCVD phenotypes.Methods and results We conducted a systematic review and meta-analysis of randomized controlled trials evaluating GLP-1 RAs or SGLT2is against placebo or standard care in ASCVD patients. Primary outcomes included MACE, defined as cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Risk ratios (RRs) with 95% confidence interval (CI) were calculated using a random-effects model. Twenty-six trials (151 789 patients) were included. Both GLP-1 RAs and SGLT2is significantly reduced MACE rates in ASCVD patients (RR 0.85; 95% CI 0.80-0.91 for both). GLP-1 RAs showed significant effectiveness in peripheral artery disease (RR 0.86; 95% CI 0.76-0.98) and post-acute cardiovascular events (RR 0.90; 95% CI 0.83-0.97). In ASCVD with heart failure, both drug classes reduced MACE (GLP-1 RAs: RR 0.73; 95% CI 0.63-0.84; SGLT2is: RR 0.86; 95% CI 0.78-0.95). SGLT2is significantly reduced MACE in ASCVD with chronic kidney disease (RR 0.84; 95% CI 0.72-0.99), particularly in severe albuminuria (RR 0.61; 95% CI 0.37-0.99).Methods and results We conducted a systematic review and meta-analysis of randomized controlled trials evaluating GLP-1 RAs or SGLT2is against placebo or standard care in ASCVD patients. Primary outcomes included MACE, defined as cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Risk ratios (RRs) with 95% confidence interval (CI) were calculated using a random-effects model. Twenty-six trials (151 789 patients) were included. Both GLP-1 RAs and SGLT2is significantly reduced MACE rates in ASCVD patients (RR 0.85; 95% CI 0.80-0.91 for both). GLP-1 RAs showed significant effectiveness in peripheral artery disease (RR 0.86; 95% CI 0.76-0.98) and post-acute cardiovascular events (RR 0.90; 95% CI 0.83-0.97). In ASCVD with heart failure, both drug classes reduced MACE (GLP-1 RAs: RR 0.73; 95% CI 0.63-0.84; SGLT2is: RR 0.86; 95% CI 0.78-0.95). SGLT2is significantly reduced MACE in ASCVD with chronic kidney disease (RR 0.84; 95% CI 0.72-0.99), particularly in severe albuminuria (RR 0.61; 95% CI 0.37-0.99).Conclusion GLP-1 RAs and SGLT2is exhibit distinct cardiovascular effectiveness profiles across ASCVD phenotypes. GLP-1 RAs show particular benefits in peripheral artery disease and post-acute cardiovascular events, while SGLT2is demonstrate unique advantages in ASCVD with comorbid chronic kidney disease. Both are effective in heart failure. These findings support tailored treatment strategies for diverse ASCVD participants based on specific comorbidities and risk factors.