(Last Updated On: July 7, 2020)

Niña A. Gabaton, MD, DPDS, Arnelfa C. Paliza, MD, FPDS, Eleanor L. Letran, MD, FPDS

Introduction: Acne vulgaris has multifactorial causes. Prolonged systemic antibiotics are often necessary because relapse of lesions occurs 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

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 six 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, and cutaneous and systemic adverse events.

Results: Forty patients were selected for the trial. Mean reduction rates of the non-inflammatory lesion counts of the two 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 (p<0.05). 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 (p<0.0001). Subjective self-assessment scores improved in both groups with comparable results. Cutaneous adverse events (erythema, pain, scaling, and dryness) were 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.

Keywords: acne vulgaris, metformin, lymecycline

Gabaton NA, Paliza AC, Letran EL. 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. Journal of the Philippine Dermatological Society 2019, 29(1), 20-47

1. Thiboutot DM. Overaview of acne and its treatment. Cutis. 2008;81(1 Suppl):3–7

2. Philippine Dermatological Society Health Information System. (2014) Top 10 diseases by prevalence (2013) [Data File]. Retrieved from http://www.pds.org.ph/pds-health-information-system

3. Yap F. The impact of acne vulgaris on the quality of life in Sarawak, Malaysia. J of Sau Soc of Dermatol and Dermatol Surg. 2011;16: 57-60

4. Weiss JS. Messages from molecules: deciphering the code. J Drugs Dermatol 2013;12 (suppl 6): s7-s72.

5. Thiboutot DM, Kraggs H, Gilliland K, Hagari S. Activity of type 1 5α-reductase is greater in the follicular infundibulum compared with the epidermis. Br J Dermatol 1997;138:166-171

6. Czernielewski J, Michel S, Bouclier M, Baker M, Hensby JC. Adapalene biochemistry and the evolution of a new topical retinoid for treatment of acne. J Eur Acad Dermatol Venereol 2001;15 (Suppl):5-12.

7. Hagemann L, Toso SM, Kitay K. et al. Anti-inflammatory actions of benzoyl peroxide: effects on the generation of reactive oxygen species by leucocytes and activity of protein kinase C and calmodulin. Br J Dermatol 1994;130:569-75

8. Leyden JJ, Preston N, et al. In-vivo effectivenss of adapalene 0.1%/benzoyl peroxide 2.5% gel on antibiotic-sensitive and resistant Propionibacterium acnes. J Clin Aesthet Dermatol 2011;4(5):22-26

9. Cunliff WJ, Satinton C, Forster RA. Topical benzoyl peroxide increases the sebum excretion rate in patients with acne. Br J Dermatol 1983;109:577-9

10. Simonart T, Dramaix M. Treatment of acne with topical antibiotics:lessons from clinical studies. British Journal of Dermatology 2005;153(2):395-403.

11. Webster G, Graber E. Antiobiotic treatment for acne vulgaris. Semin Cutan Med Surg.2008: 27:183-187

12. Dreno B, Bettoli V, Oscsendor F, Layton A, Mobacken H, Degreef H. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol 1004;14:391-9

13. Gollnick, H. et. al. Management of acne. A report from a global alliance to improve outcomes in acne. J Am Acad Dermatol. 2003; 49 (1): S1-S37.

14. Thiboutot D, Gollnick H, et al. Global Alliance to Improve Outcomes in Acne (endorsed by AAD 2013). J Am Acad Dermatol 2009;60:s1-s50

15. Coates P, Vykaman S, Eady EA et al. Prevalence of antibiotic-resistant propionibacterium on the skin of acne patients:10- year surveillance data and snapshot distribution study. Br J Dermatol. 2002;146:840-8.

16. Nishijima A, Kurokawa I. J Dermatol 2000; 27(5):318-323.

17. Margolis DJ, Bowe WP, Hoffstad O et al. Antibiotic treatment of acne may be associated with upper respiratory tract infections. Arch Dermatol 2005;141(9): 1132-6.

18. Levy RM, Huang EY, Roling D, Leyden JJ, Margolis DJ. Effect of antibiotics on the oropharyngeal flora in patients with acne. Arch Dermatol. 2003; 139(4):467–471.

19. Ross JI, Snellin AM, Carnegie E et al. Antibiotic-resistant lessons from Europe. Br J Dermatol 2003; 148(3):467-478.

20. Kubba, R et. al. Pathogenesis of acne. Indian J Dermatol Venereol Leprol.2009: S5-S8

21. Melnik, B. Acneigenic stimuli converge un phosphoinositol-3 kinase/Aky/Fox01 signal transduction. J Clin Exp Dermatol Res. 2010;1:101

22. Lolis M, Bowe W, Shalita A. Acne and systemic disease. In: Sadick N. Cutaneous Manifestations of Internal Disease. USA: Elsevier Inc; 2009:1161-1172.

23. 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

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

25. Quesada MN, Paliza A, Letran L. Double-blind randomized controlled trial on the efficacy and safety of metformin as an adjunct to doxycycline and tretinoin 0.025% cream in the treatment of moderate to severe acne vulgaris. J Phil Med Assoc. 2016;2 (95):7-21.

26. Burke BM, Cunliffe WJ. The assessment of acne vulgaris: The Leeds technique. Br J Dermatol. 1984;111:83-92.

27. Adityan B, Kumari R, Thappa DM. Scoring systems in acne vulgaris. Indian Journal of Dermatology, Venereology, and Leprology. 2009 May 1;75(3):323.

28. Finlay AY and Khan GK. Dermatology Life Quality Index (DLQI)- a simple practical measure for routine clinical use. Clinical and Experimental Dermatology.1994;19(3):210-216

29. Krentz AJ, Bailey CJ. Oral antidiabetic agents. Drugs. 2005 Feb 1;65(3):385- 411.

30. Tan JK. Adapalene 0.1% and benzoyl peroxide 2.5%: a novel combination for treatment of acne vulgaris. Skin Therapy Lett. 2009 Jul; 14(6):4-5.

31. Gold LS, Cruz A, Eichenfield L, Tan J, Jorizzo J, Kerrouche N, Dhuin JC. Effective and safe combination therapy for severe acne vulgaris: a randomized vehicle-controlled, double- blind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel with doxycycline hyclate 100 mg. Cutis. 2010;85:94-104.

32. 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.

33. Van De Kerkhop PCM, Kleinpenning MM, De Jong EMGJ, et al. Current and future treatment options for acne. J Dermatol Treat 2006;17:198-204

34. Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev 2000 Aug;21(4):363-392.

35. Lakshmi C. Hormone therapy in acne. Indian J Dermatol Venereol Leprol.2013: 79:322-337.

36. Zouboulis C, Piquero-Martin J. Update and future of systemic acne treatment. Dermatol. 2003;206:37-53.

37. Smith R, Mann N, Braue A, Makalainen H, Varigos G. A low-glycemic load diet improves symptoms in acne vulgaris patients: a randomized controlled trial. Am J of Clin Nutr. 2007;107-115.

38. Melnik, B, Dietary intervention in acne: attenuation of increased mTORC1 signaling promoted by Western diet. Dermato Endocrinol. 2012;4(1): 20-32.

39. Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ (2008). Fitzpatrick’s Dermatology in General Medicine (7th ed.). New York: McGraw- Hill; 2008.p. 2111.

40. Montagner S, Costa A. Current guidelines in the treatment of acne vulgaris: from the approach in the acute phase to maintaining the clinical benefits. Surg Cosmet Dermatol. 2010;2 (3): 205-213

41. Santos M, Balagat R, Frez M. The impact of skin disease on the quality of life of patients at the Philippine General Hospital outpatient clinic. J Phil Dermatol Soc. 2007;14(2):9-14.

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