Abstract—Type 2 Diabetes (T2D) elevates cardiovascular and renal risk, and combination therapy with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) is increasingly recommended. This review evaluates evidence from Cardiovascular Outcome Trials (CVOTs) and observational studies on the efficacy and safety of dual therapy. Across the SOUL, AMPLITUDE-O, and FLOW trials, GLP-1 RA-induced reductions in Major Adverse Cardiovascular Events (MACE) and renal outcomes remained consistent regardless of baseline SGLT2i treatment, with no additive safety concerns. In SOUL, oral semaglutide reduced MACE by 14% overall (HR, 0.86), with similar effects in participants receiving and not receiving SGLT2i at baseline (HR, 0.89 vs. 0.84; P-interaction = 0.66). Real-world data further suggest additive benefits on MACE, all-cause mortality, and heart failure with combination therapy compared to either drug alone. While the precise magnitude of additive protection awaits prospective quantification, existing evidence validates combined therapy as a safe and potentially synergistic approach to reducing cardiorenal risks in high-risk type 2 diabetes patients..
 
Keywords—GLP-1 receptor agonist, SGLT2 inhibitor, combination therapy, cardiovascular outcomes, type 2 diabetes

Cite: Xiaofan Weng, "Cardiovascular and Renal Outcomes of GLP-1 Receptor Agonist and SGLT2 Inhibitor Combination Therapy in Type 2 Diabetes: From Mechanistic Synergy to Clinical Evidence," International Journal of Pharma Medicine and Biological Sciences, Vol. 15, No. 3, pp. 85-89, 2026.

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