Respiratory Adverse Events of Weight-Loss Drugs: A Systematic Review and Meta-Analysis.
Weight-loss medications, including setmelanotide, do not appear to increase respiratory adverse events compared to placebo, but evidence for individuals with asthma is limited.
Where it sits
this study against the rest of the setmelanotide corpusSummary and findings
This systematic review and meta-analysis assessed respiratory adverse events (AEs) associated with weight-loss medications, including setmelanotide, in general populations and individuals with asthma. The study included 123 trials, with findings indicating that liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion did not show increased respiratory AEs compared to placebo. However, the evidence regarding individuals with asthma was limited.
Abstract
<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Background
This paper addresses the respiratory safety of weight-loss medications, particularly in the context of obesity and asthma, which are increasingly co-occurring conditions. Prior studies have suggested that weight loss may improve asthma outcomes, but the respiratory effects of weight-loss medications remain inadequately explored. This systematic review aims to fill that gap by evaluating respiratory AEs associated with various weight-loss drugs.
Methods
The study employed a systematic review design, searching databases such as Medline, Embase, Cochrane, and CINAHL without date or language restrictions. It included randomized controlled trials, nonrandomized comparative studies, and large, single-group studies assessing respiratory AEs of several weight-loss medications, including setmelanotide. The primary outcome was the incidence of respiratory AEs, analyzed through random-effects model-based meta-analyses.
Results
The primary endpoint showed that liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared to placebo. The incidence of nasopharyngitis was reported as high as 23.7% for liraglutide over 13-24 months, but this was not clearly linked to specific doses or indications.
Interpretation
The findings suggest that the weight-loss medications evaluated do not significantly increase respiratory AEs compared to placebo, which aligns with some prior literature indicating a favorable safety profile. However, the effect sizes for respiratory events like nasopharyngitis, while statistically significant, may not be clinically meaningful, especially given the limited evidence for individuals with asthma. Confounding factors include the small number of studies focusing on asthma and the overall low incidence of respiratory AEs.
Key findings
- 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).
- Overall, 123 studies were included, with 122 evaluating general populations and one focusing on individuals with asthma.
- Liraglutide, semaglutide, tirzepatide, and naltrexone-bupropion were not associated with increased respiratory AEs compared with placebo.
Limitations
- Evidence specifically addressing individuals with asthma was sparse.
- Insufficient data limited comparisons for other drugs.
- Only one study focused on individuals with asthma.