GLP-1 Receptor Agonists' Pulmonary Safety Profile Identified as Undefined, Prompting Systematic Review
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a rapidly expanding drug class for type 2 diabetes mellitus (T2DM) and obesity management. While their gastrointestinal adverse effects are well-characterized, the pulmonary safety profile of GLP-1 RAs remains incompletely defined. This represents a significant evidence gap, especially given the global scale of prescribing and the potential for systemic effects beyond metabolic regulation. Understanding these respiratory signals is crucial for comprehensive patient safety.
Study Design
This systematic review was conducted following PRISMA 2020 guidelines to synthesize evidence on respiratory adverse events associated with GLP-1 RA therapy in adults. Researchers searched PubMed, Embase, and Scopus from inception to January 2026. Eligible studies included randomized controlled trials (RCTs), observational cohorts (retrospective/prospective), pharmacovigilance disproportionality analyses, and case reports/series. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB2) for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies, with evidence certainty graded via the GRADE framework.
Results
This systematic review outlines its objectives to synthesize published evidence on respiratory adverse events temporally associated with GLP-1 RA therapy in adults. It aims to characterise their patterns and severity, appraise the risk of bias using validated tools like RoB2 and NOS, describe proposed pathophysiological mechanisms, and grade the certainty of evidence using the GRADE framework. The abstract highlights that the pulmonary safety profile of GLP-1 RAs is currently incompletely defined, necessitating this comprehensive review. The review's scope acknowledges the heterogeneity of available evidence, spanning case reports, pharmacovigilance analyses, and observational cohorts. > The review is framed primarily as a signal-detection and evidence-mapping exercise rather than a causal-inference analysis, acknowledging the heterogeneity of included evidence.
Key Findings
- Systematic synthesis of GLP-1 RA respiratory adverse event evidence.
- Characterization of pulmonary adverse event patterns and severity.
- Appraisal of bias risk in existing respiratory safety studies.
- Description of proposed pathophysiological mechanisms for pulmonary events.
- Grading of evidence certainty for GLP-1 RA respiratory safety signals.
Why It Matters
This systematic review is critical for GLP-1 RA users and clinicians, as it addresses a significant gap in understanding the pulmonary safety of these widely prescribed medications. By synthesizing existing evidence, it will provide a clearer picture of potential respiratory adverse events, their patterns, and severity, which is currently lacking. A defined pulmonary safety profile will enable more informed prescribing decisions and patient counseling, potentially influencing how these peptides are monitored or combined with other therapies. While not providing immediate protocol changes, the review's findings will be foundational for future safety guidelines and clinical practice, moving towards a more complete understanding of GLP-1 RA systemic effects.