In this episode of Topical Conversations, Crystal Aguh, MD, Associate Professor of Dermatology at Johns Hopkins School of Medicine, shares insights from her study investigating the potential benefits of metformin for patients with central centrifugal cicatricial alopecia (CCCA), a scarring alopecia that predominantly affects Black women. 

Understanding CCCA as a profibrotic disease 

CCCA is a form of permanent scarring alopecia, and previous research led by Dr Aguh demonstrated that it shares similarities with other fibrotic conditions including idiopathic pulmonary fibrosis, systemic sclerosis, and uterine fibroids. Notably, women with CCCA are 5 times more likely to have uterine fibroids than Black women without the condition. Based on these findings, Dr Aguh and her team aimed to explore potential treatment options that could reverse scarring. 

Metformin as a potential treatment 

Metformin, an FDA-approved treatment for diabetes, has been studied for its role in managing other fibrotic conditions. Dr Aguh noted that her initial research on the gene expression landscape of CCCA revealed a decreased expression of PRKAA2, a gene partially encoding adenosine monophosphate kinase (AMPK), which is the primary target of metformin. This discovery prompted the team to investigate whether metformin could impact the progression of CCCA. 

Case series: topical metformin shows promise 

In an initial case series, Dr Aguh applied topical metformin to patients with CCCA. Some patients experienced hair regrowth, and building on these findings, Dr Aguh introduced oral metformin into the treatment plan for 12 women with CCCA, administering a low dose of 500 mg once daily. 

Molecular and clinical impact 

Among the 12 women studied, 4 provided scalp tissue samples for analysis before and after oral metformin treatment. Bulk RNA sequencing revealed a near-reversal of several profibrotic pathways previously identified as hallmarks of CCCA. Pathways related to fibrosis decreased, while keratin-associated proteins—critical for hair growth—increased significantly. Clinically, 6 of the 12 patients experienced visible hair regrowth after 6 months of oral metformin use. 

A pilot study with future potential 

While the results are promising, Dr Aguh emphasizes that this is a pilot study. Larger clinical trials are necessary to quantify the benefits of metformin for CCCA and other scarring alopecias. Metformin is generally considered a safe medication, with common side effects such as weight loss and stomach upset, though stomach upset is less common in the extended-release formulation used in this study. Dr Aguh notes that patients with preexisting kidney disease require monitoring due to the risk of lactic acidosis. 

To learn more about metformin as a potential novel treatment option for reversing scarring and promoting hair regrowth in CCCA, read Dr Aguh’s full article here.