Empagliflozin lowers mortality, cardiorenal events even in COPD presence

Among patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), those with concomitant chronic obstructive pulmonary disease (COPD) are at higher risk of mortality and adverse cardiorenal outcomes, including heart failure (HF), according to post hoc analyses of the EMPA-REG OUTCOME trial. However, these outcomes can be prevented with empagliflozin treatment, regardless of the presence of COPD.

In a cohort of T2DM patients with established CVD, twice as many patients with COPD (n=707) were hospitalized for HF compared with those who had no COPD (n=6,313; hazard ratio [HR], 2.15, 95 percent confidence interval [CI], 1.32–3.49). [Diabetes Res Clin Pract 2022;doi:10.1016/j.diabres.2022.109837]

The COPD group also had increased risks of HF/CV death (HR, 1.60, 95 percent CI, 1.10–2.33), incident/worsening nephropathy (HR, 1.68, 95 percent CI, 1.26–2.24), all-cause hospitalization (HR, 1.44, 95 percent CI, 1.19–1.74), and all-cause death (HR, 1.60, 95 percent CI, 1.09–2.35).

Empagliflozin treatment reduced all the said clinical outcomes to a similar extent in those with and without COPD. Moreover, it produced improvements in HbA1c, weight, and systolic blood pressure, regardless of COPD.

Safety profile was consistent. Besides an increase in genital infections observed with empagliflozin irrespective of COPD, the proportion of patients who had an adverse event (AE), a serious AE, a confirmed hypoglycaemic episode, volume depletion, or acute renal failure was similar or lower with empagliflozin vs placebo both in the COPD and non-COPD groups.

“These data suggest that benefits of empagliflozin treatment in patients with T2DM and CVD are not mitigated by the presence of COPD,” according to the investigators.

“The underlying mechanisms of the cardiorenal and mortality effects of empagliflozin are not yet fully elucidated but are believed to include a reduction in plasma volume through osmotic diuresis, increase in haematocrit, decrease in vascular resistance, and improved cardiac remodeling,” they pointed out. [Diabetologia 2018;61:2108-2117; JAMA Cardiol 2021;6:836-840; Circulation 2019;140:1693-1702]

COPD poses high comorbidity burden

In EMPA-REG OUTCOME, where all patients had T2DM and established CVD, the risk of HF hospitalization was more than double in the COPD vs non-COPD group. Aside from this, approximately 50 percent of the patients with COPD were hospitalized for any cause at least once during follow-up. In the non-COPD group, less than 40 percent required a hospitalization.

These numbers, according to the investigators, suggest that COPD is associated with a high comorbidity burden, and the findings confirmed previous data that this high burden drives a poor prognosis in the COPD with T2DM and CVD population.

“Since treatment is challenging, careful assessment of these patients and consideration of morbidity- and mortality-reducing treatments is of the utmost importance,” they said. “Therefore, to improve prognosis in patients with COPD, a holistic approach that includes management of comorbidities with effective treatments is needed.”

The study was limited the lack of verification and characterization of the COPD diagnoses and the inability to report the effects on COPD-related hospitalizations separately.