A systematic review and meta-analysis comparing the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 agonists in type 2 diabetes.

Purpose: Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been shown to improve cardiovascular health. This meta-analysis aims to directly compare their cardiovascular outcomes in type 2 diabetes patients (T2DM). Methodology: We searched Medline, Scopus, Cochrane, and Web of Science from inception to August 2025 for observational studies that compared SGLT2 inhibitors and GLP-1 agonists in type 2 diabetes patients and baseline cardiovascular diseases (CVD). The primary outcomes were Major Adverse Cardiovascular Events (MACE) and heart failure (HF), while the secondary outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stroke. The pooled hazard ratio with 95% confidence interval (CI) was employed through a random-effects model, and a p-value < 0.05 was considered statistically significant. Results: Nineteen studies comprising 1,893,359 patients (1,182,641; SGLT2 inhibitors,710,718; GLP-1 agonists). Compared to GLP-1 agonist, SGLT2 inhibitor use was associated with a significant 18% reduced risk of heart failure in T2DM patients, while a non significantly reduced risk of MACE, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. In T2DM patients with pre-existing CVD, SGLT2 inhibitors showed a significant 14% reduced risk of heart failure, 10% reduced risk of myocardial infarction, and 7% borderline reduced risk of all-cause mortality compared to GLP-1 agonists. In T2DM patients without pre-existing CVD, SGLT2 inhibitors demonstrated a significant 17% reduced risk of heart failure, with a non-significant reduction in MACE, all-cause mortality, and myocardial infarction compared to GLP-1 agonists, and a non-significantly increased risk of cardiovascular mortality and stroke. Conclusion: Use of SGLT2 inhibitors was associated with a lower risk of HF in T2DM, along with a lower risk of HF, MI, and all-cause mortality with pre-existing CVD compared to GLP-1 agonists. However, high heterogeneity and a lack of RCTs warrant cautious clinical implications. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-025-01741-2.