Objective:

To evaluate the associations of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with gastrointestinal adverse events and other health outcomes in patients with type 2 diabetes or obesity.

Key Findings:

• GLP-1 RAs linked to higher odds of gastrointestinal adverse events: 2.47 for nausea, 2.78 for vomiting, and 1.94 for diarrhea, though variability across studies indicates uncertainty.
• High-quality evidence indicated GLP-1 RAs associated with lower odds of serious infections (0.89) and respiratory disease (0.85), but these associations were less certain.
• Exploratory signals for lower likelihood of fractures (0.67) and all-cause dementia (0.55), and greater likelihood of thyroid disease (1.27), with many findings remaining uncertain.
• Gastrointestinal disease outcomes and cancer associations were exploratory and did not meet high-credibility thresholds, indicating the need for caution.

Interpretation:

While GLP-1 RAs show potential associations with gastrointestinal adverse events and some health outcomes, the evidence remains uncertain and lacks high certainty, necessitating further research.

Limitations:

• Variability across studies and methodological concerns, including absence of prespecified protocols and incomplete reporting of funding sources, may impact findings.
• Many outcomes based on adverse event reporting rather than predefined endpoints, increasing risk of bias.
• Subgroup analyses based on limited studies were exploratory and should be interpreted with caution.

Conclusion:

Current evidence on GLP-1 RAs is insufficient for definitive conclusions of high certainty regarding their safety and efficacy across various health outcomes, highlighting the need for further investigation.