Effects of Metformin on Skin Inflammation and Hyperpigmentation
DOI:
https://doi.org/10.37287/ijghr.v8i6.2811Keywords:
hyperpigmentation, melanogenesis, melasma, metformin, post-inflammatory, skin inflammationAbstract
Metformin shows anti-inflammatory and antimelanogenic activity in experimental models, but the mechanisms and strength of evidence differ by context. This is relevant to hyperpigmentation, where inflammation and melanocyte activation may intersect. To synthesize evidence on metformin in cutaneous inflammation and hyperpigmentation, focusing on mechanisms, the inflammation-pigmentation interface, topical clinical data, and evidence gaps. Structured searches of PubMed/MEDLINE and Scopus were conducted from 10 September 2026 through 26 September 2026 using complementary inflammation, pigmentation, and topical/clinical search blocks. Of 433 records identified, 105 underwent detailed evaluation and 21 primary studies formed the core synthesis. Reporting followed SANRA principles. Metformin modulated NF-κB, AMPK/SIRT1-NLRP3, mTOR/p70S6K, IL-23-related, ROS, and immunometabolic pathways in experimental inflammatory models. Melanocyte studies showed inhibition of cAMP-CREB-MITF signaling, melanogenic enzymes, and melanosome transfer. Human evidence is concentrated in small, heterogeneous melasma trials; direct clinical evidence for PIH is lacking. Metformin has plausible effects on cutaneous inflammation and melanogenesis, but clinical evidence remains limited. Topical metformin should be considered investigational pending standardized formulations, pharmacokinetic data, longer safety follow-up, and adequately powered comparator trials.
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