A Novel Approach to Melasma Management: Comparative Evaluation of Topical 30% Metformin and Kligman's Regimen in Middle-Aged Women

Title: A Novel Approach to Melasma Management: Comparative Evaluation of Topical 30% Metformin and Kligman's Regimen in Middle-Aged Women Introduction: Melasma is a common acquired pigmentary disorder that primarily affects middle-aged women and leads to symmetrical brown patches on the face, causing cosmetic and psychological distress. Multiple factors contribute, including ultraviolet radiation, hormonal influences, and genetic predisposition. (1,2) Various treatment options are available for melasma, including topical depigmenting agents, chemical peels, laser therapy, and photoprotection. (2) Kligman's regimen - a combination of hydroquinone, tretinoin, and fluocinolone acetonide - remains the gold standard for treatment but has side effects like irritation, rebound pigmentation, and steroid-induced dermatoses. (3) Topical metformin, an antidiabetic agent with antioxidant and anti-melanogenic properties, (4) has recently shown potential as a safe and effective alternative. A Randomized Control Trial in 2022 compared 30% topical metformin with Kligman's regimen and found comparable efficacy with fewer adverse effects. (5) Similarly, an RCT in 2023 reported that topical metformin demonstrated equivalent improvement to hydroquinone with a favorable safety profile. (6) These findings highlight the potential of metformin as an effective topical alternative for melasma management. The present study aims to compare the efficacy and tolerability of 30% topical metformin cream with Kligman's regimen in middle-aged women with epidermal melasma.

Objectives Primary Objective To compare the efficacy, in terms of mean reduction in modified MASI (mMASI) score from baseline to 8 weeks, between patients treated with 30% topical metformin and Kligman's regimen.

Secondary Objectives To compare the proportion of patients developing adverse effects (erythema, burning, peeling, or PIH) in both treatment groups.

Operational Definitions Melasma: Symmetrical hyperpigmented macules and patches on the face diagnosed clinically by a postgraduate trainee and then confirmed by a senior consultant and further verified as epidermal or dermal type using Wood's lamp examination.

Modified MASI (mMASI): A scoring system that evaluates the area (A: 0-6) and darkness (D: 0-4) of pigmentation in four facial regions - forehead (30%), right malar (30%), left malar (30%), and chin (10%).