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GLP-1RA and the possible skin aging

Ioanna A Paschou1, Evangelia Sali2, Stavroula A Paschou2

  • 11st Department of Dermatology and Venereology, "Andreas Sygros" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Endocrine
|June 11, 2025
PubMed

Insights

Glucagon-like peptide 1 receptor agonists (GLP-1RA) can cause "Ozempic face" and accelerate skin aging. This occurs through complex mechanisms involving stem cells, oxidative stress, and reduced collagen production, not just fat loss.

Area of Science:

  • Dermatology
  • Endocrinology
  • Molecular Biology

Background:

  • Glucagon-like peptide 1 receptor agonists (GLP-1RA) are used for type 2 diabetes mellitus (T2DM) and obesity.
  • Patients report "Ozempic face" and facial aging as side effects of GLP-1RA therapy.
  • While GLP-1RA can reduce inflammation and potentially benefit skin, weight loss is not the sole cause of facial aging.

Purpose of the Study:

  • To review existing literature on the mechanisms by which GLP-1RA may influence skin aging.
  • To explore the direct and indirect effects of GLP-1RA on skin cells and aging processes.
  • To elucidate the pathophysiology behind "Ozempic face" beyond simple fat reduction.

Main Methods:

  • Literature review of studies investigating GLP-1RA effects on skin cells.
  • Analysis of data on GLP-1R expression in adipose-derived stem cells (ADSC) and fibroblasts.
  • Examination of molecular pathways including cytokine production, oxidative stress, ATP synthesis, and estrogen levels.

Main Results:

  • GLP-1RA stimulation of GLP-1R on ADSCs reduces protective cytokine production, increasing reactive oxygen species (ROS) and oxidative damage to fibroblasts.
  • GLP-1RA decreases glucose uptake by ADSCs, leading to reduced ATP production and apoptosis.
  • GLP-1RA indirectly lowers estrogen production in dermal white adipose tissue (DWAT), decreasing fibroblast collagen synthesis.
  • GLP-1RA interacts with advanced glycation end products (AGEs) and RAGE activation, contributing to skin aging.

Conclusions:

  • "Ozempic face" and facial aging are common side effects of GLP-1RA therapy.
  • These effects are multifactorial, involving direct impacts on ADSCs and fibroblasts, oxidative stress, and hormonal changes.
  • Mechanisms beyond fat loss contribute significantly to GLP-1RA-induced skin aging, requiring further elucidation.
Keywords:
AGEsAgingGLP-1RAObesitySkinType 2 diabetes

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