Objective:

To evaluate the association of semaglutide with epigenetic aging, specifically focusing on biomarkers in patients with HIV-associated lipohypertrophy.

Key Findings:

• Semaglutide was associated with lower annualized epigenetic aging estimates compared to placebo across several biomarkers, with adjusted analyses showing significant reductions.

Interpretation:

The findings suggest that semaglutide may influence DNA methylation-based biomarkers associated with biological aging in patients with HIV-associated lipohypertrophy.

Limitations:

• The epigenetic analyses were posthoc and exploratory, which limits the strength of the conclusions drawn from the findings.

Conclusion:

While semaglutide may influence biomarkers of biological aging, it does not establish clinical aging effects or improvements in aging-related outcomes; thus, prospective trials are urgently needed to explore the potential of glucagon-like peptide-1 receptor agonists as gerotherapeutics.