Topical Metformin Versus Triple Regimen for Epidermal Melasma

Melasma is an acquired hyperpigmentation disorder characterized by symmetrical brown ordark‐brown patches, most commonly affecting the centrofacial, malar, or mandibularregions of the face. Epidermal melasma is identified by enhanced contrast and sharplydefined pigmentation under Wood's lamp examination, indicating superficial epidermalmelanin deposition. The condition is particularly common among women of reproductive ageand is associated with ultraviolet exposure, heat exposure, pregnancy, hormonal factors,oral contraceptive use, and genetic susceptibility.Topical triple‐combination therapy has been widely used as a standard treatment formelasma. However, prolonged treatment may be limited by adverse effects, includingerythema, desquamation, burning, telangiectasia, and steroid‐related complications.Topical metformin has emerged as a possible alternative because experimental studiessuggest that it may reduce melanogenesis by downregulating melanogenic proteins anddecreasing expression of microphthalmia‐associated transcription factor. Previousclinical studies have reported improvement in melasma severity with topical metformin,but comparative evidence remains limited.This study is a randomized clinical trial that will be conducted in the DermatologyDepartment of Combined Military Hospital Malir Cantt, Karachi. The study aims to comparethe efficacy of topical 30% metformin with a topical triple regimen in patients withepidermal melasma. The planned sample consists of 104 participants, with 52 participantsin each treatment group. Participants will be recruited through non‐probabilityconsecutive sampling and then randomly allocated to either group using the lotterymethod.Eligible participants will include men and women aged 18‐50 years with epidermal melasmaconfirmed according to the study's operational definition. Participants must not haveused treatment for epidermal melasma during the previous month and must not haveundergone dermabrasion, laser ablation, or chemical peeling during the previous threemonths. Patients with acne vulgaris, rosacea, pregnancy, or comorbid conditions will beexcluded.After written informed consent, demographic and clinical information will be recorded,including age, sex, marital status, education, residence, employment status, duration ofmelasma, estimated daily sun exposure, treatment history, and site of facial involvement.Each participant will undergo clinical examination using a Wood's lamp, and a baselinemodified Melasma Area and Severity Index score will be calculated.Participants assigned to Group A will receive topical 30% metformin cream. Participantsassigned to Group B will receive a topical triple regimen containing 2% hydroquinone,0.05% tretinoin, and 0.01% fluocinolone acetonide. Both treatments will be applied oncedaily at night for eight consecutive weeks. All participants will be advised to apply SPF50 or higher sunscreen in the morning. Digital photographs will be taken before treatmentand after completion of therapy.The primary outcome is treatment efficacy at eight weeks. Efficacy will be measured usingthe percentage reduction in modified MASI score from baseline:Percentage reduction = [(baseline score ‐ post‐treatment score) ÷ baseline score] × 100Treatment will be classified as effective when the participant achieves a reduction of atleast 25% from the baseline modified MASI score. The modified MASI score will be recordedat the first visit and at the final assessment after eight weeks.Quantitative variables, including age, disease duration, and modified MASI scores, willbe summarized using mean and standard deviation. Qualitative variables, including sex,marital status, education, residence, sun exposure, melasma site, and efficacy, will besummarized using frequencies and percentages. The efficacy proportions of the two groupswill be compared using the chi‐square test, with a p‐value of 0.05 or less consideredstatistically significant. Stratification will be used to control for potentialconfounders such as age, sex, disease duration, marital status, education, residence, sunexposure, and site of melasma.