Efficacy and Safety of Topical Metformin vs Kligman Formula in the Treatment of Melasma: A Split-Face Study

Melasma is a frequent chronic pigmentary condition that is resistant to treatment, most commonly affecting Fitzpatrick skin types III to V.¹ Worldwide, melasma is one of the most prevalent dermatoses, varying from 9% to 50%.² The pathogenesis is due to increased melanocyte activity and melanin production, influenced by genetics, ultraviolet (UV) light, hormonal changes, and certain medications.³ The disease appears as symmetrically arranged hyperpigmented patches and macules mainly on the face.⁴ Clinically, melasma manifests as 3 facial patterns: centrofacial, malar, and mandibular. It can also be classified by Wood's lamp examination into epidermal, dermal, or mixed types based on the depth of melanin pigment.¹

The gold standard in treating melasma is Kligman's formula, containing hydroquinone (HQ), but it may cause side effects like contact dermatitis, redness, post-inflammatory hyperpigmentation, permanent depigmentation, and ochronosis.⁵ Metformin, primarily an anti-diabetic drug, has emerged as a potential treatment for melasma. It has been studied in various clinical trials for inflammatory skin conditions like hidradenitis suppurativa, acanthosis nigricans, psoriasis, acne, and allergic contact dermatitis, showing promising outcomes. In melasma, metformin reduces cyclic adenosine monophosphate (cAMP) levels, which helps lower melanin production in melanocytes by inhibiting key pathways.⁶