GLP-1 receptor agonists versus SGLT2 inhibitors in patients with coexisting COPD and heart failure

Chronic obstructive pulmonary disease (COPD) and heart failure (HF) frequently coexist, leading to elevated risks of morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated cardiopulmonary benefits, but their comparative effectiveness in patients with both conditions remains unclear. We conducted a multi-institutional, propensity-score-matched cohort study using the TriNetX research network to compare GLP-1RA and SGLT2i initiation in adults with coexisting COPD and HF. The primary outcome was all-cause mortality over one year. Secondary outcomes included all-cause hospitalization, COPD exacerbation, acute respiratory failure, pneumonia, and major adverse cardiovascular events (MACE). Subgroup analyses were performed across age, sex, HF phenotype, prior COPD exacerbation, and BMI strata. Overall, 16,437 are matched in each treatment group. During one-year follow-up, GLP-1RA use is associated with a significantly lower risk of all-cause mortality compared with SGLT2i (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.47 to 0.56). Survival benefit is consistent across all subgroups. GLP-1RA therapy also confers lower risks of all-cause hospitalization (HR, 0.84; 95% CI, 0.74 to 0.96), COPD exacerbation (HR, 0.87; 95% CI, 0.78 to 0.97), acute respiratory failure (HR, 0.65; 95% CI, 0.59 to 0.72), pneumonia (HR, 0.76; 95% CI, 0.69 to 0.85), and MACE (HR, 0.60; 95% CI, 0.54 to 0.67). In adults with coexisting COPD and HF, initiation of GLP-1RA therapy is associated with lower risks of mortality and cardiopulmonary complications compared with SGLT2i therapy. These findings may support the potential role of GLP-1RAs in managing complex cardiometabolic multimorbidity. People with COPD and heart failure often have poor health outcomes, including frequent hospitalizations and an increased risk of death. Two commonly prescribed medications, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), may provide benefits beyond blood sugar control, but it is unclear which treatment is associated with better outcomes in patients with both conditions. We analyzed electronic health records from a large international database and compared patients who started either medication. After matching patients with similar clinical characteristics, we found that those receiving GLP-1RAs have lower risks of death, hospitalization, COPD exacerbation, respiratory failure, pneumonia, and major cardiovascular events during one year of follow-up. These findings suggest that GLP-1RAs may offer important cardiopulmonary benefits in this high-risk population, although future clinical trials are needed to confirm these results. Huang et al. conduct a propensity score-matched cohort study using TriNetX to compare initiation of GLP-1 receptor agonists versus SGLT2 inhibitors in adults with coexisting COPD and heart failure. GLP-1 receptor agonists are associated with lower one-year mortality and reduced risks of hospitalization, COPD exacerbation, acute respiratory failure, pneumonia and major adverse cardiovascular events compared with SGLT2 inhibitors.