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Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review

  • Authors:
    • Ellia Nilam
    • Julia Windi Gunadi
    • Meilinah Hidayat
  • View Affiliations / Copyright

    Affiliations: Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Universitas Kristen Maranatha, Bandung, West Java 40164, Indonesia
    Copyright: © Nilam et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 96
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    Published online on: August 5, 2025
       https://doi.org/10.3892/wasj.2025.384
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Abstract

Metformin, a first‑line anti‑diabetic agent, has recently gained attention for its topical application in dermatology due to its pleiotropic pharmacological effects beyond glucose control. These include anti‑inflammatory, antioxidant, anti‑photoaging and wound‑healing properties that suggest promising roles in skin health. The present scoping review aimed to map and synthesize existing experimental and clinical evidence on mechanistic pathways and the therapeutic potential of topical metformin in dermatologic applications. A comprehensive literature search was conducted across the Scopus, Web of Science, EBSCO, and PubMed databases for studies published between 2014 and 2024, using predefined inclusion criteria including key words, such as ‘topical metformin’, ‘topical metformin and skin aging’ and ‘topical metformin and dermatologic’. Data were extracted from 19 eligible studies, including in vitro and in vivo studies and clinical trials. The findings revealed that topical metformin inhibited melanogenesis by downregulating microphthalmia‑associated transcription factor expression and related pathways, it promoted collagen synthesis and angiogenesis in wound models, and exerted anti‑photoaging effects through oxidative stress modulation and enhanced autophagy. Additionally, it exhibited antitumor activity in melanoma and clinical efficacy in treating conditions, such as melasma and acne vulgaris with minimal adverse effects. Advanced delivery systems, such as hydrogels and nanofibers, have further improved the bioavailability and therapeutic outcomes. On the whole, as demonstrated herein, topical methods have emerged as a safe, multi‑targeted agent with broad dermatological utility. Nevertheless, further well‑designed clinical trials are warranted to establish long‑term safety, optimal dosage and formulation strategies for human use. 
View Figures

Figure 1

PRISMA flow diagram for the article
selection process used in the present scoping review.

Figure 2

Mechanistic perspectives on the
dermatologic potential of topical metformin. cAMP, cyclic adenosine
monophosphate; CREB, cAMP response element-binding protein; MITF,
microphthalmia-associated transcription factor; PKC-β, protein
kinase C-β; IL, interleukin; TNF, tumor necrosis factor; FGF,
fibroblast growth factor; ROS, reactive oxygen species; MDA,
malondialdehyde; GSH, glutathione; mTOR, mammalian target of
rapamycin; AMPK, AMP-activated protein kinase; VEGF, vascular
endothelial growth factor; PARP-1, poly(ADP-ribose) polymerase 1;
RAGE, receptors for advanced glycation end products. The studies
mentioned in this figure are as follows: Lehraiki et al
(17), AboAlsoud et al
(5), Channakeshavaiah et al
(14), Mapar et al
(23), Mostafa et al
(4), Cui et al (19), Xiao et al (15), Yu et al (21), Mousa et al (20), Zhao et al (30), Tombulturk et al (31), Qing et al (32), Tombulturk et al (11), Cam et al (9), Cam et al (33), Tawfeek et al (8), Zhang et al (6), Tombulturk et al (10), Xiong et al (13).

Figure 3

Potential mechanism of topical
metformin as an anti-cancer agent.

Figure 4

Potential mechanisms of topical
metformin in wound healing.
View References

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Spandidos Publications style
Nilam E, Gunadi JW and Hidayat M: Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review. World Acad Sci J 7: 96, 2025.
APA
Nilam, E., Gunadi, J.W., & Hidayat, M. (2025). Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review. World Academy of Sciences Journal, 7, 96. https://doi.org/10.3892/wasj.2025.384
MLA
Nilam, E., Gunadi, J. W., Hidayat, M."Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review". World Academy of Sciences Journal 7.5 (2025): 96.
Chicago
Nilam, E., Gunadi, J. W., Hidayat, M."Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review". World Academy of Sciences Journal 7, no. 5 (2025): 96. https://doi.org/10.3892/wasj.2025.384
Copy and paste a formatted citation
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Spandidos Publications style
Nilam E, Gunadi JW and Hidayat M: Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review. World Acad Sci J 7: 96, 2025.
APA
Nilam, E., Gunadi, J.W., & Hidayat, M. (2025). Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review. World Academy of Sciences Journal, 7, 96. https://doi.org/10.3892/wasj.2025.384
MLA
Nilam, E., Gunadi, J. W., Hidayat, M."Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review". World Academy of Sciences Journal 7.5 (2025): 96.
Chicago
Nilam, E., Gunadi, J. W., Hidayat, M."Mechanistic perspectives on the dermatologic potential of topical metformin: A scoping review". World Academy of Sciences Journal 7, no. 5 (2025): 96. https://doi.org/10.3892/wasj.2025.384
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