If you have endometriosis, you may have heard the recent speculation around Endo-205, a mysterious new endometriosis treatment reportedly heading towards clinical trials (Gargiulo, 2026)! So I got curious and tried to find more information on the drug itself, how it functions and what the research has found so far.

While trying to understand the biology behind Endo-205, I kept coming across the Wnt signalling pathway. That led me down a bit of a research rabbit hole, because another very familiar drug has also been shown to interfere with Wnt signalling in endometriosis: metformin. The more digging I did, the more papers I found about metformin’s potential use in endometriosis treatment! So, is metformin the “missing link” in endometriosis treatment? To find out, I’m breaking down a 2022 narrative review by Kimber-Trojnar et al., which brought together the existing evidence on metformin as a potential treatment for endometriosis.

What is Metformin?

Metformin is a commonly used drug to treat type 2 diabetes mellitus, specifically to improve insulin sensitivity and reduce insulin resistance. It has been used for decades and is generally well tolerated. But metformin does more than regulate blood sugar. It has what scientists call pleiotropic effects (it can influence several biological processes at once), including inflammation, cell growth and metabolism. The review focused on four processes that metformin may influence: inflammation, angiogenesis (the formation of new blood vessels), apoptosis (programmed cell death) and cellular adhesion.

But why would a diabetes drug have anything to do with endometriosis? The review explores whether metformin could interfere with several processes that allow endometriotic lesions to survive and grow.

Metformin in Inflammation

Firstly, the researchers explored the role of metformin in inflammation. Chronic inflammation plays an important role in endometriosis, and the review identified evidence that metformin may reduce the production of inflammatory molecules in endometrial cells. For example, laboratory studies found that metformin reduced IL-8 production, a molecule involved in inflammation (Pease and Sabroe, 2002).

Metformin may also promote autophagy (the cell’s recycling system (Cleveland Clinic, 2022)) through a pathway called mTOR. Together, these findings suggest metformin could interfere with some of the inflammatory processes involved in endometriosis.

Additionally, the review found that metformin may also influence local oestrogen production. Endometriotic tissue can express aromatase, an enzyme involved in producing oestrogen. Laboratory studies included in the review found that metformin reduced aromatase activity in endometriotic cells, suggesting another potential way it could interfere with lesion growth.

Metformin in Angiogenesis

Angiogenesis refers to the formation of new blood vessels (Yao and Li, 2025), as seen in endometriotic lesions. Endometriotic lesions need a blood supply to survive and grow, making angiogenesis a potential therapeutic target. Metformin has been shown to reduce VEGF, a protein that promotes new blood-vessel formation (Shibuya, 2011). More importantly, this wasn’t just a molecular change. In rat models of endometriosis, metformin treatment was associated with reductions in the weight, area and volume of endometriotic lesions.

Metformin in Adhesion and Invasion

Moreover, the researchers also explored whether metformin could interfere with the adhesion and invasion of endometriotic tissue. The ability of endometriotic tissue to attach to surrounding structures is an important part of disease progression. In rat models, metformin treatment reduced the size of endometriotic lesions and was associated with less severe adhesions.

Metformin and Apoptosis

Lastly, endometriotic cells can also show reduced apoptosis, which is the body’s process of removing cells that are damaged or no longer needed (Cleveland Clinic, 2024). The review found evidence that metformin can increase apoptosis and restrict cell proliferation through several cellular pathways. In theory, this could make it harder for endometriotic tissue to survive and continue growing. However, much of this evidence comes from laboratory and animal studies rather than clinical trials and people with endometriosis.

And what about Wnt signalling?

Remember Wnt signalling from the beginning? One study included in the review found increased Wnt2 production in endometriotic cells. Wnt2 can activate β-catenin signalling, a pathway involved in cell growth and communication (Wu et al., 2025). Interestingly, metformin reduced Wnt2 production and subsequently reduced the growth of nearby cells. This raises an interesting possibility: metformin might interfere with some of the cellular communication that helps endometriotic tissue grow. But (and this is important), this experiment was performed on cells in the lab, not in a clinical trial.

But what about humans?

This is where the evidence becomes much sparser. The review reports some human evidence suggesting metformin may reduce endometriosis-associated symptoms and inflammatory markers, while potentially supporting ovulation and conception. However, clinical trials are rare, the available evidence is limited, and results across studies are varied. Most of the evidence still comes from cells and animal models.

What this means for endometriosis

So, is metformin really the ‘missing link’ in endometriosis treatment? Unfortunately, not yet. The laboratory and animal evidence is certainly promising, and metformin appears to influence inflammation, blood-vessel formation, cell survival, oestrogen production and signalling pathways such as Wnt/β-catenin. But this doesn’t automatically translate into effective treatment. Most of the evidence reviewed was preclinical, while clinical studies remain limited with varied results. The authors therefore call for larger, prospective clinical trials before metformin can be recommended as an endometriosis treatment. For now, metformin remains an interesting candidate for drug repurposing, not a secret hidden cure.

References

  1. Kimber-Trojnar, Ż., Dłuski, D.F., Wierzchowska-Opoka, M., Ruszała, M. and Leszczyńska-Gorzelak, B. (2022). Metformin as a Potential Treatment Option for Endometriosis. Cancers, 14(3), p.577. doi:10.3390/cancers14030577.

  2. Gargiulo, D.A. (2026). ENDO-205 and the New Wave of Non-Hormonal Endometriosis Treatments — Hope for the Future, Care for Today. [online] New England Endometriosis. Available at: https://www.newenglandendometriosis.com/education/endometriosis/endo-205-and-the-new-wave-of-non-hormonal-endometriosis-treatments-hope-for-the-future-care-for-today/ [Accessed 28 Sept. 2026].

  3. Pease, J.E. and Sabroe, I. (2002). The Role of Interleukin-8 and its Receptors in Inflammatory Lung Disease. American Journal of Respiratory Medicine, [online] 1(1), pp.19–25. doi:10.1007/BF03257159.

  4. Cleveland Clinic (2022). Autophagy: Definition, Process, Fasting & Signs. [online] Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/articles/24058-autophagy [Accessed 28 Sept. 2026].

  5. Yao, H. and Li, J. (2025). Angiogenesis and Related Disorders: Emerging Insights and Future Directions. Biomedicines, 13(11), p.2730. doi:10.3390/biomedicines13112730.

  6. Shibuya, M. (2011). Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes & Cancer, 2(12), pp.1097–1105. doi:10.1177/1947601911423031.

  7. Cleveland Clinic (2024). Apoptosis (Programmed Cell Death). [online] Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/articles/apoptosis [Accessed 28 Sept. 2026].

  8. Wu, X., Que, H., Li, Q. and Wei, X. (2025). Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy. Molecular Cancer, 24(1). doi:10.1186/s12943-025-02363-1.