Are Breztri (budesonide, glycopyrrolate, and formoterol) and Trelegy (fluticasone furoate, umeclidinium, and vilanterol) comparable inhalers for Chronic Obstructive Pulmonary Disease (COPD)?

Are Breztri and Trelegy Comparable Inhalers for COPD?

Yes, Breztri (budesonide/glycopyrrolate/formoterol) and Trelegy (fluticasone furoate/umeclidinium/vilanterol) are both effective single-inhaler triple therapies for COPD, but recent real-world evidence suggests Trelegy may have a modest advantage in reducing exacerbations and mortality. 1

Evidence-Based Comparison

Efficacy Outcomes

The most recent and highest-quality comparative effectiveness study (2025) demonstrated that Trelegy users had:

• 12% lower rate of moderate-severe COPD exacerbations compared to Breztri (0.80 vs 0.91 exacerbations per patient-year; rate ratio 0.88,95% CI 0.85-0.92) 1
• 10% lower risk of experiencing a moderate-severe exacerbation at 12 months (hazard ratio 0.90,95% CI 0.87-0.93) 1
• 11% lower risk of all-cause mortality at 12 months (5.6% vs 6.4%; hazard ratio 0.89,95% CI 0.80-0.98) 1

This real-world study of over 44,000 Medicare patients provides the strongest current evidence for choosing between these agents when prioritizing mortality and exacerbation reduction. 1

Guideline Context for Triple Therapy

Both inhalers align with the 2023 Canadian Thoracic Society strong recommendation for LAMA/LABA/ICS triple combination therapy in patients with moderate-to-severe COPD at high risk of exacerbations (≥2 moderate or ≥1 severe exacerbation in the past year). 2 Single-inhaler triple therapy is specifically favored over multiple inhalers due to increased adherence and reduced errors in inhaler technique. 2

Clinical Characteristics of Each Inhaler

Breztri (Budesonide/Glycopyrrolate/Formoterol)

• Dosing: Twice-daily administration 3
• Delivery: Pressurized metered-dose inhaler using co-suspension delivery technology 3
• Evidence: Demonstrated reductions in moderate/severe exacerbations, improved lung function, dyspnea, rescue medication use, and health-related quality of life versus dual therapies 3
• Real-world use: Commonly initiated in patients with ongoing symptoms and exacerbations despite current therapy, with 57.9% having baseline exacerbation history 4

Trelegy (Fluticasone Furoate/Umeclidinium/Vilanterol)

• Dosing: Once-daily administration 5
• Delivery: ELLIPTA dry powder inhaler 5
• Evidence: The IMPACT trial showed superior reduction in moderate-severe exacerbations, improved trough FEV1, and better quality of life compared to dual therapies 6
• Non-inferiority: Single-inhaler Trelegy is non-inferior to using two separate inhalers (FF/VI + UMEC) for lung function outcomes 7

Practical Decision Algorithm

Choose Trelegy when:

• Prioritizing maximum reduction in exacerbations and mortality risk (based on the 2025 comparative effectiveness data) 1
• Once-daily dosing is preferred for adherence 5
• Patient can effectively use a dry powder inhaler 5

Choose Breztri when:

• Patient cannot use dry powder inhalers effectively and requires a metered-dose inhaler 3
• Twice-daily dosing fits better with patient's medication schedule 3
• Cost considerations favor Breztri in specific insurance formularies

Both are appropriate when:

• Patient meets criteria for triple therapy (moderate-to-severe COPD with ≥2 moderate or ≥1 severe exacerbation in past year) 2
• Patient has persistent symptoms despite dual bronchodilator or ICS/LABA therapy 2

Important Safety Considerations

Pneumonia Risk

Both inhalers carry a 4% increased risk of pneumonia compared to bronchodilators alone, with a number needed to harm of 33 patients treated for one year. 8 Monitor particularly in patients who are current smokers, age ≥55 years, have prior exacerbations/pneumonia, BMI <25 kg/m², or severe airflow limitation. 8

Common Pitfalls to Avoid

• Never use either inhaler for acute symptom relief—they are maintenance therapies only 5
• Do not step down from triple therapy to dual therapy in high-risk patients, as withdrawing ICS increases exacerbation risk, particularly with blood eosinophils ≥300 cells/mL 8
• Do not use ICS as monotherapy—always combine with long-acting bronchodilators 8
• Avoid in patients with severe milk protein allergy (both contain lactose) 5

Monitoring Requirements

• Regular assessment for pneumonia symptoms 8
• Eye examinations for glaucoma and cataracts with long-term ICS use 5
• Bone mineral density monitoring in at-risk patients 5
• Growth velocity monitoring in pediatric patients 5

Bottom Line

While both are effective triple therapies endorsed by guidelines, the 2025 real-world comparative effectiveness study provides the strongest current evidence that Trelegy offers modest but statistically significant advantages in reducing exacerbations and mortality compared to Breztri. 1 However, both remain appropriate choices depending on individual patient factors such as inhaler device preference, dosing schedule, and formulary considerations. 2, 3, 6