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BACKGROUND Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with PCOS. However, benefits of metformin in patients with acne in general are not well established. OBJECTIVE To study effectiveness of metformin in non-PCOS acne patients and to understand the mechanisms of action of metformin in non-PCOS acne. METHODOLOGY In this observational study, 30 clinically confirmed acne vulgaris patients were treated with metformin (1000 mg/day) for three months without any other topical or systemic active intervention for acne. The effect of metformin at clinical, hormonal and genetic level was assessed. RESULTS Metformin monotherapy significantly (p#x003C;0.0001) decreased the global acne grading score for acne followed by marginal increase in insulin with a significant (p=0.028) increase in insulin-like growth factor-1 (IGF-1). A significant (p=0.0003) decrease in free androgen index resulting from a significant (p<0.0002) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. The homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box O1 (FoxO1) expression was significantly (p=0.006) downregulated upon metformin treatment at mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), squalene epoxidase and acyl CoA synthetase (p=0.0005, 0.0249, 0.0268, respectively) were also downregulated. CONCLUSION Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FoxO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.