Efficacy and Safety of Metformin for Melasma, Acne Vulgaris, and Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis of Oral and Topical Formulations
Abstract
Abstract Background: The metabolic-dermatologic axis is an emerging frontier in precision medicine. Metformin, a biguanide primarily used for Type 2 Diabetes Mellitus, acts as a potent activator of 5’ adenosine monophosphate-activated protein kinase (AMPK). Dysregulation of the AMPK/mTORC1 and AMPK/MITF signaling pathways has been implicated in the pathogenesis of hyperpigmentary and inflammatory skin disorders. While clinicians increasingly explore metformin for off-label dermatologic use, a comprehensive synthesis of clinical evidence regarding its efficacy and safety remains absent. Objective: This systematic review aims to evaluate the clinical efficacy and safety profile of oral and topical metformin across three distinct dermatologic conditions: melasma, acne vulgaris, and hidradenitis suppurativa (HS). Methods: We performed a systematic search of MEDLINE, Embase, Cochrane Central, and ClinicalTrials.gov from inception through March 2026, adhering to PRISMA 2020 guidelines. Included studies comprised randomized controlled trials (RCTs), prospective cohort studies, and high-quality case series that investigated metformin (topical gels/creams or oral formulations) against placebo or standard-of-care treatments (e.g., Kligman’s formula for melasma; topical retinoids for acne; systemic biologics or antibiotics for HS). Primary outcomes included clinical reduction in mMASI (melasma), GAGS/lesion count (acne), and HiSCR/Hurley staging (HS). Risk of bias was assessed using…
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