Real-world comparative effectiveness of triple versus and dual inhalers in chronic obstructive pulmonary disease: Impact of diabetes comorbidity

Sophia Eilat-Tsanani, Sophie Dellaniello, Pierre Ernst, Samy Suissa

Keywords: COPD, diabetes mellitus, comorbidity

Background:

The recommended first-line treatment for patients with chronic obstructive pulmonary disease (COPD) who have a history of exacerbations is single-inhaler dual bronchodilators combining long-acting muscarinic antagonists (LAMA) and long-acting beta2-agonists (LABA). Single-inhaler triple therapy, combining LAMA, LABA, and inhaled corticosteroids (ICS), is recommended for those who also have significant eosinophilia. While type 2 diabetes (T2D) is a frequent comorbidity in COPD, associated with poorer outcomes, the latest management guidelines (GOLD) recommend that the two conditions be treated independently.

Research questions:

Is there a difference in the effectiveness of treatment with single-inhaler triple versus single-inhaler dual bronchodilators with coexisting T2D.

Method:

A cohort study comparing initiators of single-inhaler triple versus dual bronchodilators on the incidence of moderate or severe exacerbation was performed using a general practice database. Weighted Cox proportional hazard models were used to estimate hazard ratios (HR), stratifying on the presence of a T2D and prior exacerbations.

Results:

The study cohort involved 33,901 patients with COPD. It included 8544 also had T2D, of which 13.3% initiated triple therapy, and 25,202 with no T2D, of which 11.7% started triple therapy. Among patients with two or more exacerbations prior to treatment, the HR of a moderate or severe exacerbation with triple therapy was 1.04 (95% CI: 0.86-1.25) in patients with T2D and 0.74 (95% CI: 0.65-0.85) in patients without diabetes.

Conclusions:

Our analyses suggest that the presence of T2D alongside COPD may affect the effectiveness of therapy. We found that the effectiveness of initiating treatment of exacerbating COPD with single-inhaler triple therapy is more effective than a dual bronchodilator at reducing the risk of exacerbation in patients without T2D, but not in patients with T2D. This study suggests avenues for future research toward a precision medicine approach to COPD management.

Points for discussion:

RCTs, like those that were brought to use single-inhaler triple medications for COPD tend to ignore patients with comorbidity in the analysis. How can we overcome this gap in our knowledge?