Liraglutide, Semaglutide, Tirzepatide, and Naltrexone-Bupropion Show No Increased Respiratory Adverse Events

The growing global prevalence of obesity often coexists with asthma, leading to a distinct "obese asthma phenotype" characterized by increased disease severity and poorer treatment outcomes. While weight loss demonstrably improves asthma outcomes, the respiratory safety profile of various effective weight-loss medications remains largely underexplored. This gap in evidence creates uncertainty for clinicians and patients, particularly concerning potential respiratory adverse events in a population already vulnerable to pulmonary issues.

Researchers conducted a systematic review and meta-analysis across Medline, Embase, Cochrane, and CINAHL, plus trial registries, without date or language restrictions. They included 123 studies (randomized controlled trials, nonrandomized comparative studies, and large single-group studies) assessing respiratory adverse events for liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, phentermine-topiramate, and setmelanotide. Risk of bias was assessed using design-specific tools, and random-effects models were used to compare risk differences for respiratory AEs between active interventions and placebo.

The comprehensive search yielded 9,086 unique records, culminating in 123 included studies, with 122 focusing on general populations and only one specifically on individuals with asthma. Overall, the randomized trials demonstrated a low risk of bias. The analysis revealed that:

Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory adverse events compared with placebo. Common respiratory AEs observed included upper respiratory tract infections and nasopharyngitis. Nasopharyngitis incidence ranged from 4.1% (95% CI: 0.7%, 9.3%; tirzepatide, 0-6 months) to over 23.7% (95% CI: 19.6%, 28.1%; liraglutide, 13-24 months). Importantly, these common events were not clearly associated with specific doses or indications. Data for other weight-loss drugs were insufficient for robust comparisons, and evidence regarding asthma patients specifically was notably sparse.