Comparison of Efficacy of Metformin Gel 30% vs Triple Combination Cream (Hydroquinone 4%, Flucinolone Acetonide 0.01%, Tretinoin 0.025%) in Treatment of Melasma in Tertiary Care Hospital Karachi

NCT07345507 | Completed

• 1 other identifier: F.2-81/2024-GENL/24/JPMC
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare two topical treatments for melasma. Participants will be randomly assigned to receive either triple combination cream (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%) or 30% metformin gel, applied once nightly for 12 weeks. All participants will use broad-spectrum sunscreen (SPF ≥30) during the daytime throughout the treatment period. Melasma severity will be assessed using the Melasma Area and Severity Index (MASI), and the study will determine which treatment is more effective and better tolerated at the end of 12 weeks.

Conditions

Melasma

Keywords

Melasma; Efficacy; METFORMIN GEL; HYDROQUINONE 2%; TRETINOIN 0.025%

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with ≥50% reduction in MASI score from baseline at 12 weeks.

  The Melasma Area and Severity Index (MASI) will be used to assess the severity of melasma. The MASI score is calculated based on the area of involvement, darkness, and homogeneity on four facial regions. Participants achieving ≥50% reduction in total MASI score from baseline at week 12 will be classified as treatment responders. Data will be reported as the number and percentage of responders in each treatment arm and compared between arms.

  12 weeks (end of treatment)

Secondary Outcomes (2)

• Mean change in MASI score from baseline to 12 weeks.

  2 weeks (end of treatment)

• Frequency of treatment-related adverse effects during the 12-week treatment period.

  12 weeks (during treatment)

Study Arms (2)

Group A (TRIPLE COMBINATION THERAPY GROUP)

ACTIVE COMPARATOR

Triple combination cream (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%) applied nightly for 12 weeks. All participants also used broad-spectrum sunscreen (SPF ≥30) during daytime.

Drug: Triple combination cream (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%); Drug: Broad-spectrum sunscreen (SPF ≥30)

Group B ( METFORMIN 30% GEL THERAPY GROUP )

EXPERIMENTAL

Participants will apply 30% metformin gel topically to melasma-affected areas once nightly for 12 weeks. All participants will also use broad-spectrum sunscreen (SPF ≥30) during daytime.

Drug: Metformin gel, 30%; Drug: Broad-spectrum sunscreen (SPF ≥30)

Interventions

Metformin gel, 30% DRUG

Participants will apply 30% metformin gel topically to melasma-affected areas once nightly for 12 weeks. All participants will also use broad-spectrum sunscreen (SPF ≥30) during daytime.

Group B ( METFORMIN 30% GEL THERAPY GROUP )

Triple combination cream (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%) DRUG

Topical triple combination cream containing hydroquinone 2%, tretinoin 0.025%, and fluocinolone acetonide 0.01%, applied once nightly to affected facial areas for 12 weeks

Group A (TRIPLE COMBINATION THERAPY GROUP)

Broad-spectrum sunscreen (SPF ≥30) DRUG

Applied during daytime throughout the 12-week treatment period (both arms)

Group A (TRIPLE COMBINATION THERAPY GROUP); Group B ( METFORMIN 30% GEL THERAPY GROUP )

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged 18- 60 years of either gender.
• Diagnosed with melasma based on clinical examination and Wood's lamp assessment.

You may not qualify if:

• Pregnant or lactating women.
• Patients with a history of hypersensitivity to any study medication components.
• Patients currently on other melasma treatments or those with other dermatologic conditions affecting pigmentation.

Sponsors & Collaborators

• Jinnah Postgraduate Medical Centre: lead

Study Sites (1)

JPMC

Karachi, Sindh, 7550, Pakistan

Location

Related Publications (24)

• Grimes PE, Pandya AG, Taylor SC, Rendon MI. Challenges in melasma treatment: need for standardization and multicenter RCTs. Dermatol Ther. 2022;35(1):e15234. doi:10.1111/dth.15234

  RESULT

• Steiner D, Pandya AG. Melasma and hormonal imbalance: an evidence-based review. J Eur Acad Dermatol Venereol. 2021;35(8):1630-40. doi:10.1111/jdv.17123

  RESULT

• Del Rosario E, Florell SR, Zone JJ. Gender and hormonal differences in melasma pathogenesis. Int J Womens Dermatol. 2023;9(2):95-103. doi:10.1016/j.ijwd.2023.02.004

  RESULT

• Coondoo A, Phiske M, Verma S, Lahiri K. Side-effects of topical steroids: A long overdue revisit. Indian Dermatol Online J. 2014 Oct;5(4):416-25. doi: 10.4103/2229-5178.142483.

  PMID: 25396122 RESULT

• Misitzis D, Georgala S, Katoulis AC. Comparison of the effectiveness and safety of triple combination cream vs hydroquinone monotherapy in melasma. J Cosmet Dermatol. 2022;21(9):3882-7. doi:10.1111/jocd.14278

  RESULT

• Frances L, Cuesta L, Leiva-Salinas M, Banuls J. Secondary mucinous carcinoma of the skin. Dermatol Online J. 2014 Apr 16;20(4):22361.

  PMID: 24746304 RESULT

• Lima EVA, Lima MA, Paixão MP, Miot HA. Assessment of the efficacy of a triple combination cream for melasma in different populations: a literature review. Clin Cosmet Investig Dermatol. 2020;13:505-10. doi:10.2147/CCID.S238536

  RESULT

• Pomeranz MK, Belsito DV. Mechanisms of postinflammatory hyperpigmentation and therapeutic strategies. Clin Dermatol. 2020;38(1):64-72. doi:10.1016/j.clindermatol.2019.06.009

  RESULT

• Lee AY. Anti-melanogenic effects of metformin: beyond diabetes. J Dermatol Sci. 2021;104(1):1-8. doi:10.1016/j.jdermsci.2021.06.002

  RESULT

• González-Pedraza A, Salazar-Aranda R, Pérez-Herrera P, Torres-Torres Y. Metformin as an adjuvant in dermatology: molecular mechanisms and clinical applications. Int J Dermatol. 2023;62(2):132-40. doi:10.1111/ijd.16391

  RESULT

• Mahmoud MMY, Kamel AM, Galal SA. Evaluation the efficacy of microneedling with topical metformin solution compared with microneedling with topical vitamin C solution in treatment of melasma. Arch Dermatol Res. 2024 Oct 5;316(9):662. doi: 10.1007/s00403-024-03355-9.

  PMID: 39369111 RESULT

• Ali Mapar M, Namdari G. Efficacy of topical metformin 15% vs placebo in melasma: RCT over 12 weeks. J Cosmet Dermatol. 2019;18(5):1357-63. doi:10.1111/jocd.12904

  RESULT

• Gan C, Rodrigues M. An Update on New and Existing Treatments for the Management of Melasma. Am J Clin Dermatol. 2024 Sep;25(5):717-733. doi: 10.1007/s40257-024-00863-2. Epub 2024 Jun 19.

  PMID: 38896402 RESULT

• AboAlsoud ES, Eldahshan RM, AbouKhodair Mohammed H, Elsaie ML. Safety and efficacy of topical metformin 30% cream versus triple combination cream (Kligman's formula) in treating melasma: A randomized controlled study. J Cosmet Dermatol. 2022 Jun;21(6):2508-2515. doi: 10.1111/jocd.14953. Epub 2022 Apr 9.

  PMID: 35357753 RESULT

• Mapar MA, Hemmati AA, Namdari G. Comparing the efficacy of topical metformin and placebo in the treatment of melasma: a randomized, double-blind clinical trial. J Pharm Res Int. 2019;30(4):1-8. doi:10.9734/JPRI/2019/v30i430276

  RESULT

• Banavase Channakeshavaiah R, Andanooru Chandrappa NK. Topical metformin in the treatment of melasma: A preliminary clinical trial. J Cosmet Dermatol. 2020 May;19(5):1161-1164. doi: 10.1111/jocd.13145. Epub 2019 Sep 10.

  PMID: 31502392 RESULT

• Mongkhon P, Ruengorn C, Awiphan R, Phosuya C, Ruanta Y, Thavorn K, Jamjanya S, Chuamanochan M, Nochaiwong S. 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.

  PMID: 38192412 RESULT

• Ahmad Nasrollahi S, Sabet Nematzadeh M, Samadi A, Ayatollahi A, Yadangi S, Abels C, Firooz A. Evaluation of the safety and efficacy of a triple combination cream (hydroquinone, tretinoin, and fluocinolone) for treatment of melasma in Middle Eastern skin. Clin Cosmet Investig Dermatol. 2019 Jun 10;12:437-444. doi: 10.2147/CCID.S202285. eCollection 2019.

  PMID: 31354327 RESULT

• Atwa MA, Ahmed AH, Nada HA, Refaey SM, Jafferany M, Elsaie ML. Combined chemical peels versus trichloroacetic acid (TCA) for treating melasma: a split face study. J Dermatolog Treat. 2022 Mar;33(2):959-964. doi: 10.1080/09546634.2020.1793888.

  PMID: 32649234 RESULT

• Passeron T. Melasma pathogenesis and updated treatment options. J Eur Acad Dermatol Venereol. 2022;36(6):859-68. doi:10.1111/jdv.18101

  RESULT

• Neagu N, Conforti C, Agozzino M, Marangi GF, Morariu SH, Pellacani G, Persichetti P, Piccolo D, Segreto F, Zalaudek I, Dianzani C. Melasma treatment: a systematic review. J Dermatolog Treat. 2022 Jun;33(4):1816-1837. doi: 10.1080/09546634.2021.1914313. Epub 2022 Mar 23.

  PMID: 33849384 RESULT

• Rahman A, Basit A, Mohsin S, Ahmed N, Tahir M, Ishfaq A. Quality of life of melasma patients in Pakistan. Pak Armed Forces Med J. 2022;72(1):307-10.

  RESULT

• Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014 Sep-Oct;89(5):771-82. doi: 10.1590/abd1806-4841.20143063.

  PMID: 25184917 RESULT

• Kang HY, Ortonne JP. Melasma update. Acta Dermatovenerol Alp Pannonica Adriat. 2009;18(2):137-42

  RESULT

MeSH Terms

Conditions

Melanosis

Interventions

hydroquinone; Tretinoin

Condition Hierarchy (Ancestors)

Hyperpigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: FCPS part 2 Trainee dermatology

Model Details: Randomized Control Trial

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: January 15, 2026
• Study Start: February 1, 2025
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

PA (1)