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

Eur Heart J Cardiovasc Pharmacother. 2025 Mar 13;11(2):174-189. doi: 10.1093/ehjcvp/pvae093.

Abstract

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).

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.

Keywords: Atherosclerotic cardiovascular disease; Comparative effectiveness; Glucagon-like peptide-1 receptor agonists; Major adverse cardiovascular events; Sodium-–glucose cotransporter-2 inhibitors.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Aged
  • Atherosclerosis* / diagnosis
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / mortality
  • Female
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Humans
  • Incretins* / adverse effects
  • Incretins* / therapeutic use
  • Male
  • Middle Aged
  • Phenotype
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Incretins
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor