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

NCT ID: NCT07345507

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-01

Study Completion Date

2025-08-30

Brief Summary

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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.

Detailed Description

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This randomized, parallel-group clinical trial will be conducted at the Department of Dermatology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, after approval from the Institutional Review Board/Ethics Committee of JPMC. Eligible patients presenting with clinically diagnosed melasma will be screened and enrolled after obtaining written informed consent.

Participants will be randomly assigned in a 1:1 ratio to one of two treatment arms using a computer-generated randomization sequence. Group A (active comparator) will receive 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 B (experimental) will receive topical metformin gel 30%, applied once nightly to melasma-affected areas for 12 weeks. All participants in both arms will be advised to apply broad-spectrum sunscreen (SPF ≥30) during daytime throughout the treatment period.

Melasma severity will be assessed using the Melasma Area and Severity Index (MASI) at baseline and during follow-up visits over the 12-week treatment period. The primary outcome will be the proportion of participants achieving at least a 50% reduction in total MASI score from baseline at week 12. Safety and tolerability will be monitored throughout the study by documenting adverse effects reported by participants or observed on clinical examination.

Conditions

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Melasma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized Control Trial
Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group A (TRIPLE COMBINATION THERAPY GROUP)

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.

Group Type ACTIVE_COMPARATOR

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

Intervention Type 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

Broad-spectrum sunscreen (SPF ≥30)

Intervention Type DRUG

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

Group B ( METFORMIN 30% GEL THERAPY GROUP )

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 Type EXPERIMENTAL

Metformin gel, 30%

Intervention Type 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.

Broad-spectrum sunscreen (SPF ≥30)

Intervention Type DRUG

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

Interventions

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Metformin gel, 30%

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.

Intervention Type DRUG

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

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

Intervention Type DRUG

Broad-spectrum sunscreen (SPF ≥30)

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jinnah Postgraduate Medical Centre

OTHER_GOV

Sponsor Role lead

Responsible Party

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Dr Summiya Shakeel Ahmed

FCPS part 2 Trainee dermatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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JPMC

Karachi, Sindh, Pakistan

Site Status

Countries

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Pakistan

References

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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

Reference Type 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

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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

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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.

Reference Type RESULT
PMID: 25396122 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 24746304 (View on PubMed)

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

Reference Type 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

Reference Type 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

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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

Reference Type 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.

Reference Type RESULT
PMID: 39369111 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 38896402 (View on PubMed)

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.

Reference Type RESULT
PMID: 35357753 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 31502392 (View on PubMed)

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.

Reference Type RESULT
PMID: 38192412 (View on PubMed)

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.

Reference Type RESULT
PMID: 31354327 (View on PubMed)

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.

Reference Type RESULT
PMID: 32649234 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 33849384 (View on PubMed)

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.

Reference Type 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.

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PMID: 25184917 (View on PubMed)

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

Reference Type RESULT

Other Identifiers

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F.2-81/2024-GENL/24/JPMC

Identifier Type: -

Identifier Source: org_study_id

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