Is Breztri (budesonide, formoterol, and glycopyrrolate) superior to Trelegy (fluticasone furoate, vilanterol, and umeclidinium) for the treatment of Chronic Obstructive Pulmonary Disease (COPD)?

Direct Head-to-Head Comparison

Based on the most recent and highest-quality real-world evidence, Trelegy (fluticasone furoate/umeclidinium/vilanterol) is superior to Breztri (budesonide/glycopyrrolate/formoterol) for COPD treatment, demonstrating a 12% lower rate of moderate-to-severe exacerbations and 11% lower all-cause mortality at 12 months. 1

Primary Effectiveness Outcomes

The 2025 comparative effectiveness study analyzing 44,542 Medicare Fee-for-Service patients provides the strongest direct comparison between these two single-inhaler triple therapies (SITT): 1

• Exacerbation rate reduction: Trelegy users experienced 0.80 exacerbations per patient-year versus 0.91 for Breztri users [Rate Ratio: 0.88 (95% CI: 0.85-0.92); P < 0.001] 1
• Risk reduction at 12 months: 10% lower risk of moderate-to-severe exacerbations with Trelegy [HR: 0.90 (95% CI: 0.87-0.93); P < 0.001] 1
• Mortality benefit: 11% lower all-cause mortality risk with Trelegy at 12 months [5.6% vs. 6.4%; HR: 0.89 (95% CI: 0.80-0.98); P = 0.020] 1

These findings remained consistent across different insurance populations (Medicare Advantage, Medicaid, commercial), strengthening the generalizability of results. 1

Clinical Context for Triple Therapy Use

Both medications are appropriate for patients with severe COPD (GOLD category D) who continue experiencing exacerbations despite dual bronchodilator therapy. 2 The American College of Chest Physicians notes the number needed to treat is four patients for one year to prevent one moderate-to-severe exacerbation with triple therapy versus dual bronchodilator therapy. 2

Patient selection criteria for either SITT: 2

• Moderate to severe COPD with FEV₁ <50-60% predicted
• History of exacerbations despite optimal bronchodilator therapy
• Inadequate symptom control on dual therapy

Safety Considerations

Pneumonia risk: Both medications contain inhaled corticosteroids, which increase pneumonia risk with a number needed to harm of 33 patients for one year, suggesting a favorable risk-benefit ratio when balanced against exacerbation prevention. 2

Cardiovascular safety: The IMPACT study (evaluating Trelegy) demonstrated good safety profile without excess cardiovascular effects, though comorbidities were frequent in the study population. 3

Tolerability: Breztri demonstrated generally similar tolerability to its individual components in pivotal trials. 4

Mechanistic and Formulation Differences

While both are once-daily triple therapies, they differ in: 3, 4

• ICS component: Fluticasone furoate (Trelegy) versus budesonide (Breztri)
• LAMA component: Umeclidinium (Trelegy) versus glycopyrronium (Breztri)
• LABA component: Vilanterol (Trelegy) versus formoterol (Breztri)
• Delivery technology: Trelegy uses Ellipta dry powder inhaler; Breztri uses Aerosphere pressurized metered-dose inhaler with co-suspension delivery technology

Evidence Quality Assessment

The 2025 comparative effectiveness study 1 represents the highest-quality direct comparison available, utilizing:

• Large sample size (>44,000 patients)
• Real-world Medicare population
• Overlap weighting with high-dimensional propensity scores to minimize confounding
• Multiple sensitivity analyses across different insurance populations
• Clinically meaningful outcomes (exacerbations, mortality)

This substantially outweighs individual pivotal trials of each medication versus their respective comparators, which did not directly compare the two SITTs. 3, 4

Common Pitfalls to Avoid

Do not assume equivalence: Despite both being triple therapies with similar mechanisms, the 12% difference in exacerbation rates and mortality benefit with Trelegy represents clinically meaningful differences. 1

Consider prior therapy: Real-world data shows 57.9% of Breztri initiators had recent exacerbations, and 54.3% had oral corticosteroid fills during the prior year, suggesting these patients had poorly controlled disease. 5 Patients switching from ICS/LABA to Trelegy demonstrated significant exacerbation reduction. 6

Device considerations: While Breztri's metered-dose inhaler may benefit patients unable to generate adequate inspiratory flow for dry powder inhalers, this should not override the mortality and exacerbation benefits demonstrated with Trelegy unless specific contraindications exist. 4, 1