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A double-blind randomized controlled trial on the efficacy and safety of metformin as an adjunct to lymecycline and topical adapalene plus benzoyl peroxide gel in the treatment of moderate to severe acne vulgaris

PHRR190320-002091

Unspecified

Unspecified

A double-blind randomized controlled trial on the efficacy and safety of metformin as an adjunct to lymecycline and topical adapalene plus benzoyl peroxide gel in the treatment of moderate to severe acne vulgaris

Acne vulgaris has multifactorial causes.  Prolonged systemic antibiotics are often necessary because relapse of lesions occur upon its discontinuation. Currently, antimicrobial resistance is a growing concern. Androgen inhibitors like metformin may decrease need for antibiotics and maintain adequate control of the disease.  Objective: To determine the efficacy and safety of metformin versus placebo as an adjunct to lymecycline and adapalene+benzoyl peroxide gel in the treatment of moderate to severe acne vulgaris. Methods: Patients with moderate to severe acne vulgaris received either metformin or placebo tablets, together with lymecycline and adapalene+benzoyl peroxide gel. Lymecycline was taken for 6 weeks. The rest were given for 18 weeks.  Evaluation was done biweekly using the mean reduction rates of non-inflammatory, inflammatory and total lesion count, modified global severity score, subjective self-assessment score, Dermatology life quality index (DLQI) score, cutaneous and systemic adverse events. Results: Forty patients were included. Mean reduction rates of the non-inflammatory lesion counts of the 2 groups were comparable (p>0.05). Mean reduction rates of the inflammatory and total lesion count in the metformin group were higher than the placebo group (p0.05). The mean modified global severity score of the metformin group was lower than the placebo group (p=0.034). Mean DLQI scores decreased in both groups (p0.0001). Subjective self-assessment scores improved in both groups with comparable results. Cutneous adverse events (erythema, pain, scaling and dryness) wer tolerable. Systemic adverse events (diarrhea, flatulence, headache and epigastric pain) were self-limited. Conclusion:  Metformin is an effective and safe adjunct in the treatment of moderate to severe acne vulgaris.

Regime Classification Priority
2010 - 2016 Health Technology Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2013-12-01 9 2014-08-31

Completed

Institution Classification Region LTO #
University of Santo Tomas Hospital Private Non-profit NCR
Institution Classification Region LTO #
University of Santo Tomas Hospital Private Non-profit NCR
Institution Region
Asian Acne Board Philippines
Name E-Mail Institution and Institution Address
Nina Gabaton nina_gabaton@yahoo.com University of Santo Tomas Hospital, Manila Philippines
Name E-Mail Institution and Institution Address
Nina Gabaton nina_gabaton@yahoo.com University of Santo Tomas Hospital, Manila, Philippines
Name Expertise Affiliation
Arnelfa C. Paliza Dermatology University of Santo Tomas Hospital
Eleanor L. Letran, MD Dermatology University of Santo Tomas Hospital
Nina A. Gabaton, MD Dermatology University of Santo Tomas Hospital
Project Location Institutional Ethics Review Board
University of Santo Tomas Hospital University of Santo Tomas Hospital Institutional Review Board
University of Santo Tomas Hospital University of Santo Tomas Hospital Institutional Review Board
University of Santo Tomas Hospital University of Santo Tomas Hospital Institutional Review Board

Acne vulgaris

The primary objective of this study was to determine the efficacy and safety of metformin versus placebo in combination with lymecycline and adapalene 0.1% + benzoyl peroxide 2.5% gel in the treatment of moderate to severe acne vulgaris. Specifically, it aimed to determine and compare the improvement of acne lesions in both treatment groups through the evaluation of the following: the mean reduction rate of the non-inflammatory, inflammatory and total lesion count, based on the Leeds Acne Lesion Counting System, the improvement of the modified global severity score, the improvement in severity as reported by the patient during each follow-up visits using the subjective self-assessment score of change, the improvement in the quality of life as reported by the patient using the Dermatology Life Quality Index (DLQI) scores before and after treatment. 

The grading of cutaneous adverse events (erythema, pain, scaling and dryness) reported by the patient and/or observed by the investigator. Incidence and frequency of systemic adverse events reported by the patient such as allergy, diarrhea, nausea, vomiting, abdominal pain,  and others.

Completed

  • Philippines

Clinical Trial

Unspecified

00

2013-08-15

0000-00-00

34

40

possible future participant exclusions from the study

2013-12-01

Patients selected for this study were males and females, aged 16 to 45 years old, diagnosed with moderate to severe acne by the primary investigator, with a modified global severity score of 2 to 4. (Appendix B) Patients with history of hypersensitivity to tetracycline, metformin, benzoyl peroxide or adapalene; diabetes mellitus; renal; cardiac and hepatic diseases; alcoholism; serious infection; severe diarrhea or vomiting; fever; poor oral intake; conditions predisposing to tissue anoxia; and females with pregnancy or polycystic ovaries were excluded from the study. Wash-out periods for topical treatment on the face were observed as follows: 2 weeks for corticosteroids, antibiotics, antibacterials, antiseptics, retinoids, other anti-inflammatory drugs or other acne treatments, 1 week for phototherapy devices for acne and cosmetic procedures. For systemic treatment, wash-out periods were observed as follow:  4 weeks for antibiotics, 6 months for other acne treatments, 6 months for oral contraceptive pills, and 3 months for antiandrogens such as spironolactone/drospirenone.

Interventional

Metformin

Metformin is an agent commonly used for the treatment of non insulin-dependent diabetes mellitus. It has been used in patients with polycystic ovarian syndrome resulting in improvement of the skin manifestations of hyperandrogenemia. In a study by Kolodziejczyk et al21 administration of metformin 500mg three times a day or 3 months resulted in reduction of acne score by 14%.  It has been shown to significantly decrease insulin levels and hyperandrogenism.22 A decrease in androgen levels will inhibit seborrhea, lipogenesis and follicular hyperkeratinization, subsequently decreasing the formation of acne lesions. Prolonged intake of metformin is well-tolerated by many patients with minimal side effects. It is therefore, valuable to determine if it can serve as an adjunct treatment in patients with moderate to severe acne vulgaris to help limit the duration of the intake of oral antibiotics and avoid quick relapse upon discontinuation of these antibiotics. Its efficacy as an adjunct may ultimately contribute to lessen the possibility of development of antimicrobial resistance.

Date Amendment Classification Reason
2014-07-03 Amendments related to the protocol Design of trial

Randomized

Double Blind

Subjects were randomized using the block randomization technique. Patients were randomly assigned a study number in the order that they were recruited, and assigned to either the metformin (M) group or placebo (P) group by a secondary investigator. The patients, as well as the primary investigator who assessed them at baseline and during their follow-up visits, were blinded to the treatment being given.

Parallel

To determine the efficacy and safety of metformin versus placebo in combination with lymecycline and adapalene 0.1% + benzoyl peroxide 2.5% gel in the treatment of moderate to severe acne vulgaris.

Phase I/II

Utilization Utilization Info
Publication

None

Oral Presentation

22nd Philippine Dermatological Society Residents’ Annual Research Forum, Crowne Plaza, Ortigas, November 19, 2014

Drug Literature

Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril. 2000 Jun; 73(6): 1149- 1154

Harborne, L et al. Metformin or antiandrigen n the treatment of hirsutism in polycystic ovary syndrome. L Clin Endocrinol and Metab. 2003; 88: 4116

Siapno IP & Letran EL. (2009). Phase II clinical trial on the efficacy of metformin as an adjunct to topical tretinoin in the treatment of acne vulgaris. Unpublished manuscript.

Posters

E- poster Festival, University of Santo Tomas Hospital,November 14, 2014

E- poster, American Academy of Dermatology, Washington, DC, USA March 2016

E-poster, World Congress of Dermatology, Singapore, April 2016

Others

Recipient of the Asian Acne Board 2013 Research Grant Program

Recipient of the 2016 Strauss and Katz World Congress Fund Scholarship (American Academy of Dermatology)

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