Oral Metformin for Treating Dermatological Diseases: A Systematic Review

August 2020 | Volume 19 | Issue 8 | Original Article | 713 | Copyright © August 2020


Published online July 24, 2020

Calvin T. Sung MBAa,b, Tiffany Chao BSa,b, Alfred Lee MDb, Delila Pouldar Foulad MDa, Franchesca Choi BS RPha, Margit Juhasz MDa, Allison Dobry MDa, Natasha Atanaskova Mesinkovska MD PhDa

aUniversity of California, Irvine, Department of Dermatology, Irvine, CA BUniversity of California, Riverside, School of Medicine, Riverside, CA

Abstract

Introduction:Metformin is an antihyperglycemic medication most commonly used to treat Type II Diabetes Mellitus with promising off-label application for the treatment of hidradenitis suppurativa, psoriasis, acne, acanthosis nigricans, and hirsutism.
Objective: To comprehensively assess evidence regarding the use of metformin for treating primary cutaneous disorders.
Materials and Methods: A systematic literature search was conducted through PubMed, Cochrane, Web of Science, and CINAHL to identify the role of metformin in primary skin disease.
Results: Sixty-four studies met inclusion criteria. Metformin demonstrates promising clinical response and favorable safety profile for treatment of HS, with most patients experiencing a decrease in frequency or severity of HS flares, and some experiencing full resolution of HS lesions. Patients with psoriasis treated with metformin experienced quantifiable clinical responses. Application of metformin on polycystic ovarian disease (PCOS) related acne, acanthosis nigricans, and hirsutism yielded mixed clinical results. No serious adverse effects were reported.
Conclusion: Metformin is safe and efficacious and may be considered as an adjunctive therapy for the treatment of psoriasis and hidradenitis suppurativa in addition to first line therapies as well as PCOS related acne, acanthosis nigricans, and hirsutism.

J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4874

INTRODUCTION

Although metformin is typically employed as a first-line agent for treatment of type II diabetes mellitus (T2DM), it is being increasingly utilized as a therapy for a variety of other conditions including metabolic syndrome, polycystic ovary syndrome (PCOS), hyperandrogenism, and even cancer prevention. Metformin lowers insulin resistance by suppressing hepatic gluconeogenesis while stimulating skeletal myocyte glucose uptake and inhibiting the proinflammatory response and targeting hyperandrogenism. Given its reassuring safety profile, metformin has been increasingly considered for treating diseases associated with inflammatory and metabolic syndrome such as psoriasis, hidradenitis suppurativa (HS), acne, hirsutism, and acanthosis nigricans.

The mechanism of action of metformin is complex and incompletely understood. Metformin is theorized to act primarily via inhibition of mitochondrial function, generating an ATP-deficient environment leading to activation of AMP-activated protein kinase (AMPK) and upregulation of catabolic metabolism. Metformin also dampens the pro-inflammatory response by inhibiting nuclear factor kappa-B (NFκB) via both liver-associated AMPK-dependent and independent pathways, and down-regulates production of nitric oxide (NO), prostaglandin E2 (PGE2), and acute inflammatory markers TNF-α, IL-1, and IL-6. Finally, metformin has been shown to decrease hyperandrogenism, and thought to directly affect hormonal steroidogenesis by modulating ovarian and adrenal androgen output.

While further research to elucidate metformin’s myriad downstream effects is needed, metformin remains a promising clinical therapy for dermatologic disease. This systematic review will explore the clinical efficacy of metformin treating various dermatologic conditions, including HS, psoriasis, acanthosis nigricans, acne, and hirsutism.

MATERIALS AND METHODS

Literature Search
This study was done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).1 A primary literature search was conducted with the databases PubMed, Cochrane, Web of Science, and CINAHL. Two authors independently screened the above-mentioned databases. The search terms used are as follows: PubMed and Cochrane: (metformin OR glucophage OR dimethylguanylguanidine OR dimethylbiguanidine) AND (skin and connective tissue diseases