Metformin and Melasma: Topical Metformin as a Treatment Option

Original Article: Safety and efficacy of topical metformin 30% cream versus triple combination cream (Kligman's formula) in treating melasma: A randomized controlled study

What are the key takeaways of this article?

Melasma is an acquired common pigmentary condition that generally presents as pigmented macules on the face and most often affects women. As of now, the exact mechanism of pathogenesis for melasma has not been elucidated. Triple combination creams (TCC), also commonly known as Kligman's formula, are regarded as the mainstay of treatment for moderate to severe melasma. TCC are compounded by specialty pharmacies and generally contain a combination of hydroquinone, tretinoin, and a corticosteroid. Unfortunately, while these ingredients are quite effective together, they also all have their own associated adverse effects with long-term use.

Though it is primarily known as an oral antidiabetic medication, metformin has recently been studied topically for its melanopenic effects and potential use in melasma. Currently, there are no commercially available preparations of topical metformin and this medication must be compounded by a reliable pharmacy specialized in such preparations, which may present some difficulty. However, topical metformin has already been noted to be beneficial in conditions such as hormonal acne, hidradenitis suppurativa, and acanthosis nigricans. Its downregulation of melanogenesis makes topical metformin an interesting drug of study for dermatologic disorders involving hyperpigmentation.

In this randomized controlled trial by AboAlsoud et al., 40 patients over 18 years of age with clinically diagnosed melasma were recruited and divided into two groups; one group used topical metformin 30% cream while the other used a TCC preparation of hydroquinone 2% + tretinoin 0.025% + fluocinolone acetate 0.01%. Both creams were used once daily at bedtime. To be included, participants had to have abstained from topical and systemic melasma treatments for one month prior to the study and had to have not received any kind of cosmetic procedure, such as laser ablation or dermabrasion, for 3 months prior to the study. Pigmentation severity and improvements were assessed using the melasma area severity index (MASI) at baseline and after 8 weeks of using treatment. Unfortunately, the skin color of the participants were not included within the study.

Interestingly, the MASI score decreased significantly from 12.18 ± 9.33 before treatment to 5.59 ± 4.61 at Week 8 for the topical metformin group (p = 0.001) and from 16.05 ± 8.73 to 7.54 ± 5.77 for the TCC group (p = 0.001). No significant difference was reported between the two treatment modalities regarding the reduction in melasma throughout the study period (p = 0.968).

While no adverse effects were reported in the metformin group, in the TCC group, only one participant noted redness and a burning sensation upon application of the cream and only 3 participants experienced irritation. However, it is important to note that adverse effects were not found to be statistically significant between both groups.

In summary, topical metformin cream in a concentration of 30% weight:volume is a safe and potentially effective treatment for melasma, though the use of this medication still needs to be verified by long-term and large-scale studies in different populations.

Publication Date: June 16th, 2024

Reference: AboAlsoud ES, Eldahshan RM, AbouKhodair Mohammed H, Elsaie ML. Safety and efficacy of topical metformin 30% cream versus triple combination cream (Kligman's formula) in treating melasma: A randomized controlled study. J Cosmet Dermatol. 2022;21(6):2508-2515. doi:10.1111/jocd.14953

Summary By: Taylor Skinner