A recent retrospective case series suggests that metformin, a commonly prescribed medication for type 2 diabetes, may also significantly improve symptoms and promote hair regrowth in Black women suffering from treatment-refractory central centrifugal cicatricial alopecia (CCCA). CCCA is a chronic inflammatory hair disorder that leads to permanent hair loss, predominantly affecting Black women.
Study Overview
The case series, conducted at the Johns Hopkins University Alopecia Clinic, involved 12 Black women aged between their 30s and 50s, all diagnosed with biopsy-confirmed, treatment-resistant CCCA. These participants had previously undergone various standard treatments for at least six months but experienced stagnant or worsening symptoms before metformin (500 mg extended-release daily) was added to their regimen. Previous treatments included topical clobetasol, compounded minoxidil, and platelet-rich plasma injections.
Scalp biopsies from four participants were analyzed before and after the metformin treatment to observe gene expression changes. Researchers focused on evaluating clinical symptoms such as inflammation, scalp pain, pruritus (itchiness), scalp resistance, and hair regrowth.
Metformin Key Findings
The study revealed that metformin led to notable clinical improvements in eight out of the 12 patients. Significant reductions were observed in symptoms such as scalp pain, pruritus, inflammation, and scalp resistance. However, two patients reported a worsening of their condition. Importantly, six patients experienced hair regrowth after six months of metformin use, although one patient saw a reversal of the benefits three months after stopping treatment.
Transcriptomic analysis of the scalp biopsies identified **34 upregulated genes**, including 23 keratin-associated proteins involved in the hair growth cycle and pathways related to keratinization and epidermis development. In contrast, **eight genes were downregulated**, affecting pathways linked to extracellular matrix organization and collagen metabolism.
Gene set variation analysis demonstrated reduced expression of inflammatory pathways, particularly T helper 17 cells and epithelial-mesenchymal transition pathways, alongside elevated signaling related to adenosine monophosphate kinase and keratin-associated proteins.
Mechanism of Action
Researchers believe that **metformin’s dual action on both fibrosis and inflammation** offers a plausible explanation for its therapeutic effects in CCCA and possibly other fibrosing alopecia disorders. These mechanisms may help address the underlying chronic inflammation and tissue scarring that contribute to hair loss in CCCA patients.
Limitations and Future Directions
Despite the promising findings, the study had notable limitations, including its small sample size, lack of a placebo control group, and the single-center, retrospective design, which may reduce the generalizability of the results. Additionally, the absence of a standardized activity or severity scale for CCCA further complicates the comparison of clinical and transcriptomic changes. Larger prospective, placebo-controlled randomized trials will be needed to rigorously assess metformin’s efficacy and establish optimal dosing for CCCA and other cicatricial alopecia disorders.
While metformin shows potential as an adjunctive treatment for CCCA, more extensive research is necessary to confirm its benefits. This study highlights the drug’s possible role in managing difficult-to-treat forms of alopecia, offering hope for those affected by this chronic condition.
The study, led by Aaron Bao from the Department of Dermatology at Johns Hopkins University School of Medicine, was published online in *JAMA Dermatology* on September 4, 2023.
Clinical Implications
Metformin could represent a novel approach to managing CCCA, particularly in patients unresponsive to conventional treatments. However, clinicians should remain cautious until more robust data is available from larger, controlled trials.