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semaglutide gip agonist case report 2026-04-23 EuropePMC

Semaglutide Linked to Unexplained High CO2 in Patient with Healthy Lungs

Unexplained hypercapnia with normal pulmonary evaluation in a patient receiving semaglutide: a diagnostic challenge

Background

Semaglutide, a GLP-1 receptor agonist (a class of drugs that mimic a natural hormone to regulate blood sugar and appetite), is widely used for type 2 diabetes and obesity. While generally well-tolerated, its impact on respiratory physiology, particularly in cases of unexplained hypercapnia (elevated carbon dioxide in the blood), is not fully understood. This study addresses the knowledge gap regarding potential respiratory side effects of semaglutide in patients with otherwise normal pulmonary function.

Results

The patient presented with symptoms of fatigue and dyspnea, and arterial blood gas analysis revealed a significant increase in partial pressure of carbon dioxide (PaCO2). Despite extensive workup, no other cause for the elevated PaCO2 was identified, and all pulmonary function tests remained within normal limits. Following the discontinuation of semaglutide, the patient's PaCO2 levels normalized, decreasing to 42 mmHg within 2 weeks, and her symptoms fully resolved. A subsequent re-challenge with a lower dose of semaglutide (0.5 mg weekly) led to a recurrence of hypercapnia (PaCO2 of 60 mmHg), further strengthening the association. Upon semaglutide initiation, the patient's PaCO2 rose from a baseline of 40 mmHg to 65 mmHg within 4 weeks, indicating severe hypercapnia.

Why It Matters

This case report highlights a rare but significant potential adverse effect of semaglutide, suggesting it may induce hypercapnia in susceptible individuals even with normal lung function. This finding underscores the importance for clinicians to consider semaglutide as a potential cause of unexplained hypercapnia in patients. Further research, including larger observational studies and potentially controlled trials, is warranted to investigate the prevalence and mechanism of this adverse event, which could lead to updated prescribing guidelines or monitoring recommendations.


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Source: europepmc:epmc_PMC13100657 · Ingested 2026-04-23 · Digest: gemini-2.5-flash