Respiratory Adverse Events of Weight-Loss Drugs: A Systematic Review and Meta-Analysis.

BACKGROUND: The coexistence of obesity and asthma is increasingly common and associated with poorer asthma outcomes. Weight loss has been shown to improve asthma outcomes. Although several effective weight-loss medications are available, evidence regarding their respiratory effects remains limited. OBJECTIVE: To conduct a systematic review of the respiratory adverse events (AEs) associated with weight-loss medications in general populations and specifically among individuals with asthma. METHODS: We searched Medline, Embase, Cochrane, and CINAHL, as well as trial registries, without date or language restrictions. We included randomized controlled trials, nonrandomized comparative studies, and large, single-group studies assessing the respiratory AEs of liraglutide, semaglutide, tirzepatide, orlistat, naltrexone-bupropion, phentermine-topiramate, and setmelanotide. We assessed the risk of bias in each study using design-specific, validated tools. We conducted random-effects model-based meta-analyses of risk differences for respiratory AEs, comparing active interventions and placebo. RESULTS: Our searches yielded 9,086 unique records. We included 123 studies, of which 122 studies evaluated general populations and one study specifically evaluated individuals with asthma. Overall, the randomized trials had low risk of bias. Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared with placebo. Insufficient data limited comparisons for other drugs. Respiratory events, such as upper respiratory tract infections and nasopharyngitis, were common, with nasopharyngitis incidence ranging 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), although these were not clearly associated with doses or indications. Evidence specifically addressing individuals with asthma was sparse. CONCLUSIONS: There was no evidence of increased respiratory harm associated with weight-loss drugs compared with placebo, suggesting a reassuring respiratory safety profile in the general population. However, evidence specifically focused on individuals with asthma remains limited.