A post-hoc analysis found that empagliflozin consistently reduced mortality and cardiorenal outcomes among patients with type 2 diabetes (T2D) and cardiovascular disease (CVD) regardless of chronic obstructive pulmonary disease (COPD) status. These findings were published in Diabetes Research and Clinical Practice.
Data from the EMPA-REG OUTCOME trial (ClinicalTrials.gov Identifier: NCT01131676) were analyzed in this study. Patients (N=7020) with comorbid T2D and CVD were randomly assigned to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. For this analysis, the effect of empagliflozin on cardiorenal outcomes was evaluated among the subset of patients with comorbid COPD.
The mean ages of the cohorts with COPD (n=707) vs without COPD (n=6313) were 65.1±8.3 and 62.9±8.7 years, respectively; 27.4% and 28.7% were women, 82.6% and 71.2% were White, body mass index (BMI) was 32.52±5.35 kg/m2 and 30.41±5.21 kg/m2, glycated hemoglobin was 8.0±0.8% and 8.1±0.9%, 83.5% and 74.7% had coronary artery disease, 17.3% and 9.3% had heart failure (HF), 57.0% and 41.7% used diuretics, and 87.1% and 80.3% used lipid-lowering agents, respectively.
Among the COPD cohort, 462 were randomly assigned to receive empagliflozin and 245 were randomly assigned to receive placebo.
Among the placebo recipients, COPD was associated with increased risk for first HF hospitalization (hazard ratio [HR], 2.15; 95% CI, 1.32-3.49), incident or worsening nephropathy (HR, 1.68; 95% CI, 1.26-2.24), composite of first HF hospitalization or CV death (HR, 1.60; 95% CI, 1.10-2.33), all-cause mortality (HR, 1.60; 95% CI, 1.09-2.35), and all-cause hospitalization (HR, 1.44; 95% CI, 1.19-1.74) but not cv death (HR, 1.23; 95% CI, 0.74-2.03) or 3-point-major adverse CV events (HR, 1.10; 95% CI, 0.77-1.57).
In comparative analysis, no significant interactions between study endpoints and COPD were observed, and empagliflozin was favored among patients with and without COPD.
Empagliflozin was also associated with reduced glycated hemoglobin, body weight, and systolic blood pressure compared with baseline among the subset of patients with COPD.
In general, the subset of patients with COPD reported more adverse events (95.0-95.1%) than the subset of patients without COPD (89.7-91.3%), but event rates did not differ between active and placebo interventions.
Similar trends were observed in sensitivity analysis using only a narrow definition of COPD.
The major limitation of this post-hoc analysis was the reliance on investigator-reported COPD diagnoses and the lack of data about disease severity or lung function.
The study authors concluded that cardiorenal outcomes were poorer among patients with T2D, CVD, and COPD comorbidities, but that empagliflozin decreased risks consistently among all patients with T2D and CVD, regardless of COPD status. These findings suggest that the benefits of empagliflozin were not mitigated by COPD.
Disclosure: Multiple authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please refer to the original article for a full list of disclosures.
Anker SD, Sander L-E, Fitchett DH, et al. Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease. Diabetes Res Clin Pract. Published online March 18, 2022. doi:10.1016/j.diabres.2022.109837