Metformin hydrochloride

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

- Principle of test: Human Application/Efficacy Test, Randomized controlled study to investigate topically applied metformin in the treatment of melasma.
- Short description of test conditions: 20 volunteers are treated daily with a 30% metformin lotion for 8 weeks (open application at the face)
- Parameters analysed / observed: Adverse effects (erythema, edema)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Metformin hydrochloride

EC Number:

214-230-6

EC Name:

Metformin hydrochloride

Cas Number:

1115-70-4

Molecular formula:

C4H11N5.ClH

IUPAC Name:

N,N-dimethylimidodicarbonimidic diamide hydrochloride

Test material form:

solid: bulk

Remarks:

migrated information: powder

Method

Type of population:

other: patients with Melasma (pigmentary disorder of the facial skin)

Ethical approval:

confirmed, but no further information available

Subjects:

- Number of subjects exposed:
- Sex: female (N = 16) male(N 0 4)
- Age: 23 - 84 years
Pregnant and lactating women; patients on oral contraceptives, phenytoin, with renal dysfunction, who were allergic to the medications under trial; and acne vulgaris and rosacea patients were excluded from the study.

Clinical history:

Patients with melasma of more than 18 years of age, who were not on any medications for melasma since at least 2 weeks for topical therapy, 1 month for systemic steroids, 3 months for cosmetic procedures such as laser, dermabrasion, or peels, were included.

Controls:

Another group of 20 patients was treated with TCC (hydroquinone + steroid + tretinoin). No negative control.

Route of administration:

dermal

Details on study design:

TYPE OF TEST USED: open application test (epicutaneous test)

ADMINISTRATION
- Type of application: open
- Vehicle / solvent: Ethanol/propylene glycol (70:30, w:w)
- Concentrations: 30%
- Volume applied: not provided (thin film)
- Testing/scoring schedule: not specified
- Removal of test substance: no


EXAMINATIONS
- Grading/Scoring system: adverse effects
- Statistical analysis: No

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: No adverse effects observed

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 20
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

RESULT: Based on the results of this study, there is no indication of an allergic potential of Metformin

Applicant's summary and conclusion

Conclusions:

Based on the results of this study, there is no indication of a sensitizing potential of Metformin.

Executive summary:

Aims: The aim of this study was to evaluate the safety and efficacy of topical metformin in the treatment of melasma, a pegmentary disorder of the facial skin, and to compare its efficacy with TCC (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%).

Methods: This was a randomized controlled study conducted on 40 patients with melasma aged more than 18 years. Patients in group 1 (n = 20) were treated with 30% metformin lotion, whereas group 2 patients (n = 20) were treated with TCC for 8 weeks. Pigmentation was assessed using Melasma Area and Severity Index (MASI) at baseline and after 8 weeks. Outcome measures included global improvement scale (grades 1‐4) and patient satisfaction. Safety was assessed according to adverse events and patch testing.

Results: All 40 patients completed the study. Out of 20 patients in group 1, 11 showed grade 1 improvement (1% to <25%) and grade 2 (25%‐50%) and grade 3 (>50%‐75%) improvements were seen in one patient each. In group 2, grades 1, 2, 3, and 4 improvements were seen in 14, 2, 1, and 1 patients, respectively. However, the difference was not statistically significant.

Adverse events were noted in three patients in group 2 and none in group 1, i.e. no adverse effects were observed in the group of patients treated with a 30% Metformin formulation.

Conclusion: Topical metformin is a novel, safe, and almost as effective modality as TCC to treat melasma. Based on the results of this study, there is no indication of a sensitizing potential of Metformin.