Objective:

To evaluate the efficacy and safety of oral small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D) and obesity.

Approach:

• Meta-Analysis: Conducted a systematic literature search and meta-analysis of randomized controlled trials assessing oral small-molecule GLP-1RAs in adults with T2D or obesity.

Key Findings:

• Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09), body mass index (MD=-2.39, 95%CI:-3.02 to -1.77), waist circumference (MD=-4.62, 95%CI:-6.09 to -3.16), fasting blood glucose (MD=-24.59, 95%CI:-28.80 to -20.37), and HbA1c (MD=-0.94, 95%CI: -1.09 to -0.79).
• Increased likelihood of achieving weight loss of ≥5% (RR=2.68, 95%CI: 2.24 to 3.20), ≥10% (RR=4.14, 95%CI: 3.19 to 5.36), and ≥15% (RR=10.61, 95%CI: 7.76 to 14.49).
• Increased treatment-emergent adverse events (RR=1.09, 95%CI: 1.06 to 1.12) and overall adverse events (RR=2.75, 95%CI: 2.41 to 3.15), particularly gastrointestinal events.
• Serious adverse events were not significantly increased (RR=1.15, 95%CI: 0.93 to 1.43).

Interpretation:

Oral small-molecule GLP-1RAs provide significant benefits in weight reduction and glycemic control, supporting their potential role as effective oral incretin therapies.

Limitations:

• The meta-analysis included only ten studies.
• Potential for publication bias and variability in study designs.

Conclusion:

Oral small-molecule GLP-1RAs offer significant metabolic benefits but require careful consideration of gastrointestinal adverse events.