OR integumentary system OR dermatology OR hair OR nail OR skin); CINAHL: ((MM "Skin and Connective Tissue Diseases+") OR (MM "Skin+") OR "skin" OR "hair" OR "nail" OR "dermatology") AND ((MM "Metformin") OR "metformin" OR "glucophage" OR "dimethylguanylguanidine" OR "dimethylbiguanidine"); Web of Science: (metformin OR glucophage OR dimethylguanylguanidine OR dimethylbiguanidine) AND (dermatology OR hair OR nail OR skin). Medical Subject Headings (MeSH®) controlled vocabulary and text words were both utilized to develop the search terms. Systematic literature search was conducted on November 26, 2018 and all articles from the beginning of the databases through that date were eligible for inclusion.
Study Selection and Appraisal
Two reviewers independently screened all article titles and abstracts to include clinical trials, cohort studies, case-control studies, case series, cross-sectional studies, or case reports, written in English, of metformin in human subjects with skin diseases. Animal studies and articles not written in English were excluded. Subsequently identified studies were then subjected to full-text review. Authors were contacted for missing data. Bias risk and methodological quality were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Rationales for exclusion and article appraisals were recorded at every stage. Final decision on study selection was reached by discussion. References of included and excluded studies were reviewed for potential studies not identified through initial search strategy.
Data Extraction and Analysis
Included studies were summarized using a data extraction form. Studies were graded using the Oxford Center for Evidence- Based Medicine 2011 Levels of Evidence.
RESULTS
Initially, 754 non-duplicate articles from the years 1969 to 2018 were identified through the above-mentioned search terms across the four literatures databases. After title/abstract screening, 104 articles met criteria for inclusion. These articles were subjected to full-text screen and 64 studies were included in this systematic review as depicted by the PRISMA flow diagram (Figure 1).
Hidradenitis Suppurativa
Oral metformin as treatment for HS has been described only in one prospective cohort study and two case reports (total n=27, age: 17–50 years) with promising clinical response and favorable safety profile.
In one prospective cohort study, 25 patients with HS who were metformin-naive were treated with metformin over 24 weeks, and clinical severity of HS was assessed with both Sartorius and Dermatology Life Quality Index (DLQI) scores obtained at 0, 12, and 24 weeks.2 Seventy-six percent of patients (n=19) showed steady improvement of their HS lesions, and 24% (n=6) showed no response. The average number of work days lost was reduced from 1.5 to 0.4 and the number of patients that were classified as severely depressed decreased from eleven to four over the treatment period.
Khandalavala’s case report described a 19-year-old female with history of PCOS since puberty and an eight-year history of cicatricial HS previously treated unsuccessfully with numerous surgical and medical interventions. After three years of multifactorial treatment with lifestyle modification, oral contraception, dapsone 100mg/day, finasteride 5mg/day, subcutaneous liraglutide, and adding metformin 2000mg/ day, the patient was free of new lesions for six months. Study reported complete healing of the axillary lesions, >90% improvement of lesions in her groin, thigh, and perianal region, and 60% improvement of lesions in her thorax and abdomen. Additionally, the patient tolerated treatment without adverse effects.3
In another case report, a 50-year-old female with history of seronegative arthritis, T2DM, and 18-year history of HS was stable while on metformin for her T2DM. However, she experienced an HS flare when metformin was discontinued after successful glycemic control through diet. The patient subsequently initiated metformin 500mg/day and noted less frequent and shorter HS flares after three months. At this point, her metformin dose was increased to 1000mg/day, which led to the resolution of her axillary sinuses and leaking abscess along with decreased pain.4
Hidradenitis Suppurativa
Oral metformin as treatment for HS has been described only in one prospective cohort study and two case reports (total n=27, age: 17–50 years) with promising clinical response and favorable safety profile.
In one prospective cohort study, 25 patients with HS who were metformin-naive were treated with metformin over 24 weeks, and clinical severity of HS was assessed with both Sartorius and Dermatology Life Quality Index (DLQI) scores obtained at 0, 12, and 24 weeks.2 Seventy-six percent of patients (n=19) showed steady improvement of their HS lesions, and 24% (n=6) showed no response. The average number of work days lost was reduced from 1.5 to 0.4 and the number of patients that were classified as severely depressed decreased from eleven to four over the treatment period.
Khandalavala’s case report described a 19-year-old female with history of PCOS since puberty and an eight-year history of cicatricial HS previously treated unsuccessfully with numerous surgical and medical interventions. After three years of multifactorial treatment with lifestyle modification, oral contraception, dapsone 100mg/day, finasteride 5mg/day, subcutaneous liraglutide, and adding metformin 2000mg/ day, the patient was free of new lesions for six months. Study reported complete healing of the axillary lesions, >90% improvement of lesions in her groin, thigh, and perianal region, and 60% improvement of lesions in her thorax and abdomen. Additionally, the patient tolerated treatment without adverse effects.3
In another case report, a 50-year-old female with history of seronegative arthritis, T2DM, and 18-year history of HS was stable while on metformin for her T2DM. However, she experienced an HS flare when metformin was discontinued after successful glycemic control through diet. The patient subsequently initiated metformin 500mg/day and noted less frequent and shorter HS flares after three months. At this point, her metformin dose was increased to 1000mg/day, which led to the resolution of her axillary sinuses and leaking abscess along with decreased pain.4
