Weight-Loss Medications Not Linked to Higher Respiratory Adverse Event Risk, Meta-Analysis Finds

Among individuals using liraglutide查看药品详情, semaglutide查看药品详情, tirzepatide查看药品详情, or naltrexone-bupropion (搜索)搜索该药品, the risk for respiratory adverse events did not differ from placebo, according to findings published in Annals of the American Thoracic Society. The systematic review and meta-analysis, led by Ian J. Saldanha, MBBS, MPH, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, and Lijuan Zeng, MHS, PhD, examined 122 studies to determine the respiratory safety profile of widely used weight-loss medications.

"The available evidence does not suggest an increased risk of common respiratory adverse events with several widely used weight-loss medications, particularly GLP-1 and dual GLP-1/GIP receptor (搜索)搜索该靶点 agonists," Saldanha and Zeng told Healio in a statement. "This may be helpful when clinicians are considering these therapies for patients with obesity (搜索)搜索该疾病 who are also concerned about respiratory side effects."

Study Design and Scope

After searching four databases and two clinical trial registries, the researchers examined 122 studies—comprising 116 randomized controlled trials, two pooled analyses, two large single-group studies, one comparative study, and one nonrandomized controlled trial—to evaluate the risk for respiratory adverse events across different weight-loss medication classes, including GLP-1 receptor (搜索)搜索该靶点 agonists, dual GIP/GLP-1 receptor agonists, lipase inhibitors, melanocortin-4 receptor agonists, and combination therapies versus placebo.

The weight-loss medications evaluated included liraglutide查看药品详情 (n = 53 studies), semaglutide查看药品详情 (Ozempic/Wegovy, Novo Nordisk查看公司主页; n = 37), tirzepatide查看药品详情 (Mounjaro/Zepbound, Eli Lilly查看公司主页; n = 16), orlistat (n = 6), naltrexone-bupropion (搜索)搜索该药品 (Contrave, Currax Pharmaceuticals; n = 5), phentermine-topiramate (n = 4), and setmelanotide (Imcivree, Rhythm Pharmaceuticals; n = 1).

Key Findings on Respiratory Safety

In studies assessing liraglutide查看药品详情, semaglutide查看药品详情, and tirzepatide查看药品详情 (GLP-1 and dual GLP-1/GIP receptor (搜索)搜索该靶点 agonists) versus placebo, the risk difference for lower respiratory tract infections—including bronchitis, pneumonia, and viral pneumonia—as well as respiratory tract infections, cough, and other respiratory harms did not significantly differ between groups.

For upper respiratory tract infections such as nasopharyngitis, sinusitis, rhinitis, and pharyngitis, most risk differences between the GLP-1 and dual GLP-1/GIP receptor (搜索)搜索该靶点 agonist group and the placebo group did not significantly differ. Two exceptions emerged: sinusitis at 0 to 6 months (risk difference, −1%; 95% CI, −1.9% to −0.1%) and rhinitis at 13 to 24 months (−0.7%; 95% CI, −1.1% to −0.2%). The researchers cautioned that these findings "should be interpreted with caution, given the potential for spurious significance due to multiple comparisons arising from the large number of outcomes and time periods evaluated."

When broken down by individual medication and dose, researchers found no elevated risk for respiratory adverse events with the most common liraglutide查看药品详情 doses (1.2 mg, 1.8 mg, and 3 mg), semaglutide查看药品详情 doses (1 mg, 2.4 mg, and 14 mg), tirzepatide查看药品详情 doses (5 mg, 10 mg, and 15 mg), or naltrexone-bupropion (搜索)搜索该药品 (32 mg/360 mg) versus placebo. Data on orlistat, phentermine-topiramate, and setmelanotide were limited and "precluded summaries," according to the study.

"The overall findings were reassuring," Zeng and Saldanha said. "Across 123 studies, including 116 randomized controlled trials, we did not find evidence that liraglutide查看药品详情, semaglutide查看药品详情, tirzepatide查看药品详情 or naltrexone-bupropion (搜索)搜索该药品 increased the risk of respiratory adverse events compared with placebo."

Incidence Patterns Over Time

The researchers observed that the incidence of nasopharyngitis with liraglutide查看药品详情 increased with longer study durations, rising from 8% at 0 to 6 months to 15.7% at 7 to 12 months and 23.7% at 13 to 24 months. A similar pattern was reported for semaglutide查看药品详情, with nasopharyngitis incidence climbing from 7.2% at 0 to 6 months to 11.9% at 7 to 12 months and 12.5% at 13 to 24 months. In contrast, nasopharyngitis incidence with tirzepatide查看药品详情 did not follow this pattern (4.1% at 0 to 6 months; 8.9% at 7 to 12 months; 4.2% at 13 to 24 months).

Evidence Gap in Asthma Populations

The review identified only one additional study—an open-label randomized controlled trial—that specifically focused on individuals with obesity (搜索)搜索该疾病 and asthma (搜索)搜索该疾病. Notably, respiratory adverse events were not reported in that study.

"At the same time, the evidence is much more limited for patients with respiratory diseases, such as asthma (搜索)搜索该疾病 or COPD (搜索)搜索该疾病, so our findings should not be interpreted as establishing either respiratory benefit or safety specifically within asthma populations," Zeng and Saldanha said.

The researchers emphasized the clinical relevance of this gap. "Obesity (搜索)搜索该疾病 and asthma (搜索)搜索该疾病 commonly coexist, and people with both conditions often have more difficult-to-control asthma and poorer outcomes," they noted. "Weight loss can improve asthma outcomes, and several highly effective medications are now available for weight management. At the same time, there has been growing interest in whether some of these medications, particularly GLP-1 receptor (搜索)搜索该靶点 agonists, may also have effects on respiratory health."

Implications for Future Research

Zeng and Saldanha called for weight-loss medication studies to systematically report respiratory outcomes, particularly in individuals with obesity (搜索)搜索该疾病 and asthma (搜索)搜索该疾病. "In studies involving people with asthma, outcomes such as asthma exacerbations, symptom control, medication use, lung function and respiratory healthcare utilization should be systematically collected and reported," they said.

They also highlighted the need for mechanistic clarity. "There is also a need for studies that can better determine whether any potential respiratory benefits of GLP-1 therapies are explained primarily by weight loss and improved metabolic health, or whether these medications may also have more direct effects on airway inflammation and respiratory disease," they continued.

"Given the increasing interest in these medications in respiratory disease, this represents an important evidence gap," Zeng and Saldanha added.