Beyond Single-Class Therapy: Real-World Combined Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2...

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) exert complementary metabolic effects and have independently demonstrated cardiovascular benefits in individuals with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD). However, despite growing evidence suggesting potential additive benefits in high-risk populations, real-world data on dual therapy remain limited. This study aimed to identify clinical factors associated with the use of combined GLP-1RA/SGLT2i therapy in routine practice.

This retrospective observational study included 202 adults with T2DM and established ASCVD admitted to a tertiary care hospital between November and December 2025. Patients were categorized according to their pre-admission outpatient regimen into four groups: neither therapy, GLP-1RA only, SGLT2i only, and combined therapy. Clinical characteristics and comorbidities were recorded at admission. Multinomial logistic regression analysis was performed to identify factors associated with treatment allocation.

Among 202 patients, 54.5% were not receiving either class, 10.9% were treated with GLP-1RA only, 21.3% with SGLT2i only, and 13.4% with both. In adjusted analyses, combined therapy was independently associated with younger age [odds ratio (OR) 0.89 per year, 95% confidence interval (CI) 0.84-0.95, p < 0.001], presence of heart failure (OR 9.64, 95% CI 2.65-35.04, p < 0.001), and insulin use (OR 10.99, 95% CI 3.12-38.72, p < 0.001). Chronic kidney disease and polyvascular disease were not associated with dual therapy use.

In this real-world cohort of patients with T2DM and ASCVD, more than half were not receiving a cardioprotective glucose-lowering therapy. Combined GLP-1RA/SGLT2i therapy was infrequently prescribed and was associated with selected clinical characteristics rather than overall cardiorenal risk burden. These findings highlight an opportunity to better align treatment strategies with a comprehensive risk-based approach.