Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis

Pajaree Mongkhon; Chidchanok Ruengorn; Ratanaporn Awiphan; Chabaphai Phosuya; Yongyuth Ruanta; Kednapa Thavorn; Sirinda Jamjanya; Mati Chuamanochan; Surapon Nochaiwong

doi:10.3389/fphar.2023.1281050

Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis

Front Pharmacol. 2023 Dec 13:14:1281050. doi: 10.3389/fphar.2023.1281050. eCollection 2023.

Authors

Pajaree Mongkhon^{1

2}, Chidchanok Ruengorn^{2

3}, Ratanaporn Awiphan^{2

3}, Chabaphai Phosuya^{2

3}, Yongyuth Ruanta^{2

3}, Kednapa Thavorn^{2

4

5

6}, Sirinda Jamjanya⁷, Mati Chuamanochan^{2

8}, Surapon Nochaiwong^{2

3}

Affiliations

¹ Pharmacoepidemiology, Social and Administrative Pharmacy (PSAP) Research Unit, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.
² Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
³ Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
⁴ Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Institute of Clinical and Evaluative Sciences, ICES uOttawa, Ottawa, ON, Canada.
⁶ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁷ Institute of Dermatology, Bangkok, Thailand.
⁸ Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Abstract

Objective: Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma. Methods: MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results: Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; n = 60; MD, -0.56; 95% CI, -1.07 to -0.04; p = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; n = 80; MD, 0.19, 95% CI, -0.25 to 0.63; p = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found. Conclusion: Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required. Systematic Review Registration: Identifier PROSPERO (CRD42022351966).

Keywords: melasma; meta-analysis; metformin; pigmentation; triple combined cream.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from the Pharmacoepidemiology and Statistics Research Center through Chiang Mai University. This work was also partially supported by grant 056-2566 from the Faculty of Medicine, Chiang Mai University, Thailand. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.