Combination therapy with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in heart failure patients with type 2 diabetes

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cardiovascular outcomes in type 2 diabetes (T2D), and SGLT2i reduces events in heart failure (HF). However, the benefit of their combination in patients with both conditions remains unclear. This study assessed the risk of all-cause death and hospitalization with combination therapy versus SGLT2i monotherapy. RESEARCH DESIGN AND METHODS: This multicenter, retrospective, observational study used the TriNetX database between January 1, 2018, and December 31, 2021. We identified 928,981 patients aged ≥18 years with HF and T2D. Of these, 168,422 received an SGLT2i. The exposure group comprised patients who initiated a GLP-1 RA within 6 months of SGLT2i initiation, while the control group included those who did not receive a GLP-1 RA after SGLT2i initiation. The index date was defined as 6 months after SGLT2i. 25,989 patients received SGLT2i and GLP-1 RA and 54,619 received SGLT2i monotherapy. Following propensity score matching, each group comprised 23,240 patients. RESULTS: Over 1 year, the risk of all-cause death in patients who received SGLT2i and GLP-1 RA relative to those who received SGLT2i monotherapy was significantly lower (2.8% vs 6.3%, p<0.001; HR 0.43; 95% CI 0.39 to 0.48). Similarly, the risk of hospitalization in patients who received SGLT2i and GLP-1 RA was also lower (32.9% vs 36.4%, p<0.001; HR, 0.87; 95% CI 0.84 to 0.90). CONCLUSIONS: The risk of all-cause death and hospitalization in patients who received combination therapy with SGLT2i and GLP-1 RA relative to those who received SGLT2i monotherapy was significantly lower in patients with HF and T2D.