Using GLP-1 agonist drugs has a number of detrimental consequences to human skin, including inhibiting the proliferation, differentiation, and metabolic acitivty of human adipose mesenchymal stem cells (ADSCs). To restore ADSC activity and mimic their activity in the skin, NeoGenesis Recovery, containing the molecules secreted from metaboloically active ADSCs, should be applied to the face to prevent and remediate the negative consequnces of GLP-1 agonists on the skin and its ADSCs.

“Ozempic face” and facial aging have been observed as side effects in many patients after glucagon like peptide 1 receptor agonists (GLP-1RA) therapy for type 2 diabetes mellitus (T2DM) and obesity. While recent studies have found that GLP-1 agonists help the patient reduce weight, and that they also help people with obesity lower their high blood pressure and reduce their odds of heart attacks or strokes, many people are now using GLP-1 agonists just to lose weight. Some physicians are doling these drugs out like candy and all the person wanting them has to do is go online and a physician will sell you the drug. It’s big business and the drug companies can’t keep up with the demand and as a result are raising their prices. So many people taking these drugs means that many, many people are experiencing the negative side-effects of GLP-1 agonists, including a face so sunken that they become unregonizable.

The rapid weight loss observed with GLP-1RA has been implicated in facial aging. However, recent evidence suggests further pathophysiological mechanisms for this side effect beyond just weight loss.

For example, GLP-1RAs were shown to significantly and effectively inhibit the in vitro proliferation and adipogenic differentiation of ADSCs within a few days of exposure, while simultaneously enhancing the production of adiponectin (increases insulin sensitivity) and increasing the fatty acid oxidation (Increasing energy) in adipose tissue. The inhibition of mature adipocyte formation was shown to reduce the presence and activity of fibroblasts in regenerating dermis. Further, in ADSCs, glucose uptake was significantly reduced; the absence of glucose in the ADSCs results in a deficiency of adenosine triphosphate (ATP), leading to cellular dysfunction, damage, aging, and apoptosis of precursor cells.

Importantly, human adipose tissue-derived stem cells (ADSC) secretome display various therapeutically relevant effects in regenerative medicine, such as induction of angiogenesis and tissue repair and regeneration. The benefits of ADSC secretome are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in host cells (Silveira et al, 2022); this means the ADSC secretome not only provides benefit to other cells, such as dermal fibroblasts and adipocytes, but also to the ADSCs themselves through autocrine effects.

Also, Wang et al. 2024 reviewed how ADSC-derived exosomes regulate inflammatory signaling within adipose tissue, with distinct cargo compared to mature adipocyte exosomes. ADSC exosomes contain anti-inflammatory miRNAs (miR-21, miR-24, miR-26) that modulate macrophage polarization and cytokine production within adipose tissue.

While there are some clear benefits to the skin in some patients using GLP-1 agonists such as reducing Advanced Glycation Endproducts (AGEs), there are a number of detrimental effects, such as reduced function of ADSCs and fibroblasts, that can be mitigated or prevented by using NeoGenesis Recovery, containing ADSC secretome.

References

Cantini G, Di Franco A, Samavat J, Forti G, Mannucci E, Luconi M. Effect of liraglutide on proliferation and differentiation of human adipose stem cells. Mol Cell Endocrinol. 2015 Feb 15;402:43-50.

Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS. Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes. J Menopausal Med. 2015 Aug;21(2):93-103. 

Ridha Z, Sabrina Guillen Fabi, Raheel Zubair, Steven H Dayan, Decoding the Implications of Glucagon-like Peptide-1 Receptor Agonists on Accelerated Facial and Skin Aging, Aesthetic Surgery Journal, Volume 44, Issue 11, November 2024, Pages NP809–NP818,

Silveira BM, Ribeiro TO, Freitas RS, Carreira ACO, Gonçalves MS, Sogayar M, Meyer R, Birbrair A, Fortuna V. Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair. PLoS One. 2022 Dec 19;17(12):e0277863

Wang Y, Li Q, Zhou S and Tan P (2024) Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes. Front. Endocrinol. 15:1374715.