Microneedling-Assisted Metformin, Tranexamic Acid, and Modified Kligman's Formula for Melasma

Microneedling-Assisted Delivery of Metformin, Tranexamic Acid, and Modified Kligman's Formula for Melasma Treatment: A Clinical and Microscopic Evaluation

Melasma is a common skin condition characterized by brown or gray patches on sun-exposed areas of the face. Although several topical treatments are available, treatment outcomes are often unsatisfactory, and recurrence is common. This randomized, parallel-group clinical trial aims to compare the efficacy and safety of microneedling-assisted topical metformin, topical tranexamic acid, and modified Kligman's formula with microneedling-assisted saline in adult women with melasma. Eighty participants will be randomly assigned to one of four treatment groups. The primary outcome is the change in Melasma Area and Severity Index (MASI) score from baseline to the end of follow-up. Secondary outcomes include clinical improvement, dermoscopic changes in pigmentation and vascular features, patient satisfaction, and treatment-related adverse events.

Study Overview

• Status: Enrolling by invitation
• Conditions: Melasma (Facial Melasma)
• Intervention / Treatment: Drug: Metformin 30% Topical Lotion; Drug: Tranexamic Acid 0.5% Topical Solution; Drug: Modified Kligman's Formula; Other: Normal Saline

Detailed Description

Melasma is a chronic acquired hyperpigmentation disorder characterized by symmetric brown to gray-brown macules and patches affecting sun-exposed areas of the skin, particularly the face. It predominantly affects women of reproductive age and has a considerable negative impact on quality of life. The pathogenesis of melasma is multifactorial, involving genetic predisposition, ultraviolet radiation, hormonal influences, increased melanogenesis, vascular alterations, and inflammatory pathways. Despite the availability of multiple treatment options, recurrence is common and no universally effective therapy has been established.

Microneedling is a minimally invasive procedure that enhances transdermal drug delivery by creating controlled microchannels within the skin, thereby improving the penetration and bioavailability of topical agents. Topical metformin has recently emerged as a potential depigmenting agent through inhibition of melanogenesis and reduction of tyrosinase activity. Tranexamic acid inhibits ultraviolet-induced melanogenesis by suppressing the plasminogen-plasmin pathway and reducing melanocyte activation. Modified Kligman's formula, consisting of hydroquinone, tretinoin, and a topical corticosteroid, remains the standard topical treatment for melasma but is frequently associated with local adverse effects.

This prospective, randomized, parallel-group clinical trial was designed to compare the efficacy and safety of microneedling-assisted topical metformin, topical tranexamic acid, modified Kligman's formula, and saline as a control in women with melasma. Eighty eligible participants were randomly allocated in a 1:1:1:1 ratio to one of four treatment groups. All participants underwent standardized microneedling using a dermapen before application of the assigned topical treatment. Treatment sessions were performed every two weeks for a maximum of five sessions, followed by a three-month follow-up period.

The primary objective was to evaluate changes in the Melasma Area and Severity Index (MASI). Secondary objectives included assessment of clinical improvement, dermoscopic changes in pigmentation and vascular features, patient satisfaction, and treatment-related adverse events. The findings of this study are expected to provide comparative evidence regarding the effectiveness and safety of these microneedling-assisted topical therapies and help optimize treatment strategies for patients with melasma.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Tanta, Egypt
    • Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female participants aged 18 years or older.
• Clinical diagnosis of melasma.
• No medical treatment for melasma during the previous 6 months.
• Willing and able to comply with all study procedures and follow-up visits.
• Provided written informed consent before study participation.

Exclusion Criteria:

• Pregnant or breastfeeding women.
• Use of hormonal contraceptives.
• Use of medications known to affect skin pigmentation (e.g., phenytoin, amiodarone, antipsychotics, cytotoxic agents, tetracyclines, or heavy metals).
• History of keloid formation or foreign body reaction.
• Known allergy or hypersensitivity to any study medication.
• Presence of systemic diseases affecting pigmentation, including hepatic, renal, thyroid, or other endocrine disorders.
• Fitzpatrick skin types V or VI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microneedling + Topical Metformin; Participants underwent standardized microneedling using a dermapen followed by topical application of 3 mL of 30% metformin lotion during each treatment session. Five treatment sessions were performed at 2-week intervals.	Drug: Metformin 30% Topical Lotion; Participants received topical metformin 30% lotion immediately after standardized microneedling with a dermapen. Approximately 3 mL of the lotion was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
Experimental: Microneedling + Topical Tranexamic Acid; Participants underwent standardized microneedling using a dermapen followed by topical application of 3 mL of 0.5% tranexamic acid solution during each treatment session. Five treatment sessions were performed at 2-week intervals.	Drug: Tranexamic Acid 0.5% Topical Solution; Participants received topical tranexamic acid 0.5% solution immediately after standardized microneedling with a dermapen. Approximately 3 mL of the solution was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
Experimental: Microneedling + Modified Kligman's Formula; Participants underwent standardized microneedling using a dermapen followed by topical application of modified Kligman's formula (hydroquinone 4%, tretinoin 0.05%, and mometasone furoate 0.1%) during each treatment session. Five treatment sessions were performed at 2-week intervals.	Drug: Modified Kligman's Formula; Participants received modified Kligman's formula consisting of hydroquinone 4%, tretinoin 0.05%, and mometasone furoate 0.1% immediately after standardized microneedling with a dermapen. Approximately 3 mL was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
Placebo Comparator: Microneedling + Saline; Participants underwent standardized microneedling using a dermapen followed by topical application of 3 mL of normal saline during each treatment session. Five treatment sessions were performed at 2-week intervals.	Other: Normal Saline; Participants received topical normal saline immediately after standardized microneedling with a dermapen. Approximately 3 mL of saline was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the saline on the skin for 4 hours before washing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Melasma Area and Severity Index (MASI) Score	Baseline to 3 months after the final treatment session (approximately 5 months after randomization)

Collaborators and Investigators

• Sponsor: Sameh Sarsik

Study record dates

Study Major Dates

• Study Start (Estimated): July 10, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Metformin; Melasma; Microneedling; Hydroquinone; Tranexamic Acid; Modified Kligman's Formula
• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hyperpigmentation; Skin and Connective Tissue Diseases; Melanosis; Organic Chemicals; Pharmaceutical Preparations; Carboxylic Acids; Crystalloid Solutions; Isotonic Solutions; Biguanides; Guanidines; Amidines; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Tranexamic Acid; Metformin; Saline Solution; Solutions
• Other Study ID Numbers: TU-DERM-MEL-2020-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No