Psoriasis
The role of metformin in the treatment and prevention of psoriasis has been studied in three RCTs and one retrospective cohort study (n=73,550). Patients were treated with 1,000 to 1,700mg/day oral metformin. All studies demonstrated positive results in both genders and throughout all age groups.
Singh et al conducted two randomized, open-label, placebocontrolled, single-center trials involving treatment of psoriasis with metformin. The initial study evaluated the efficacy and safety of insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome, outcomes for which were evaluated by psoriasis area and severity index (PASI, 0-72) and erythema, scaling, and induration (ESI, 0-9) scores. The primary endpoints were changes in PASI, ESI, and physician global assessment (PGA) scores from baseline after 12 weeks of therapy as compared to placebo. Secondary endpoints included the proportion of patients achieving 75% decrease in PASI and ESI scores in each group. The metformin group had significant improvement in PASI (P=0.001), ESI (P=0.016), and PGA (P=0.012) scores. It should be noted that both metformin and pioglitazone treatment groups had a statistically significant proportion of patients achieving 75% decrease in PASI (P=0.001, P=0.001) and ESI (P=0.001, P=0.001) without any adverse events.5
Singh et al’s more recent study (n=35) investigated the efficacy and safety of metformin in psoriasis patients with metabolic syndrome. Significant improvement in mean percent change of ESI score was observed in the metformin group (P=0.048), whereas no significant percent change was observed in PASI (P=0.215) or PGA scores (P=0.070). There was no statistically significant difference in adverse events between groups with the exception of >1kg weight gain in the placebo group (P=0.042).6
A randomized single-blind clinical trial (n=58) investigated efficacy and safety of metformin as an adjunct to methotrexate for treatment psoriatic arthritis (PsA). A significantly higher percentage (41%; n=12 of 29) of the metformin group achieved an 20% improvement in tender and swollen joints (ACR20) at 24 weeks compared to the placebo group (21%; n=6 of 29; (P<0.001), with greater improvement in Health Assessment Questionnaire- Disability Index (HAQ-DI) (P<0.005), higher PASI75 (P<0.001), and improvements in psoriatic arthritis response criteria (PsARC) score (P<0.001) at week 24 compared to placebo. There was no significant difference in adverse events between groups.7
A case-control study (n=73,404) using the United Kingdom General Practice Research Database (GPRD) to identify patients with a first-time diagnosis of psoriasis and identical number of control subjects, demonstrated that patients who received ≥15 prescriptions of metformin had reduced psoriasis risk (OR 0.77, 95% CI 0.62–0.96).8
Acanthosis Nigricans (AN)
The utility of metformin to treat AN in both male and female patients (n=57), age range, 12–45 years old, has been reported in five case reports, one RCT, two prospective cohorts, one retrospective cohort, and one case series. Various doses have been studied in adult patients ranging from 500 to 2000mg daily, as well as weight-based dosing at 25mg/kg/day.9 Metformin was noted to be an efficacious treatment for AN in 72.2% of patients. Oral metformin was also effective in AN in conjunction with isotretinoin titrated to 40–80mg/day for 2 years, 1.01 units/kg recombinant human insulin-life growth factor (rhIGF1) injections for 5 years, or a carbohydrate-controlled diet for 3 months.9-11 When compared to other diabetes medications, such as rosiglitazone, patients on metformin had greater improvement in skin texture with minimal clinical response.12
Acne
The utility of metformin as a treatment for acne has been described in 11 RCTs and 9 cohort studies. Women with a history of PCOS with acne, and one study involving men with refractory acne, (total n=1,587 patients) were treated with oral metformin (dose range, 1,000–2,550mg/day). All except three studies13-15 reported significant improvement in acne in female patients with PCOS. Only Fabbrocini et al’s study assessed the effects of metformin and a low glycemic diet on male subjects with resistant acne.16 While the study led to statistically significant improvement in acne in the experimental group receiving metformin and undergoing low glycemic diet (P<0.05), the low sample size (n=20) and lack of stratification necessitates followup studies. Metformin was generally well tolerated with the exception of gastrointestinal intolerance (nausea, vomiting, diarrhea, loss of appetite), with only few patients discontinued the studies.17,18 Although dosage correlation studies were not performed, both obese and lean patients (31.8 vs 11.6%; all P<0.017) with insulin resistance benefited from their metformin treatments over a 6-month period with dose adjustment ranging from 500–1000mg.19,20
No improvement was noted in three studies.18,21,22,23,24 Adding metformin did not lead to significant improvement in acne patients with clinical manifestations of hyperandrogenism and elevated DHEAS experienced a significant decrease in acne score by 14% (P<0.0005).21 Adding metformin to estrogen and anti-androgen medications (ie, cyproterone acetate or EE-CA) failed to significantly improve acne (P=0.79), suggesting a lack of pharmacological synergy.18,22,23,24 Both Navali et al’ and Fruzzetti et al’s studies demonstrated that statins (20mg/day simvastatin and 4 g/day myo-inositol, respectively) are superior to 1.5g/ day metformin for treating acne (P<0.05) among other PCOS parameters.15,25 Combination therapy of metformin 850mg with pioglitazone 7.5mg daily, flutamide 62.5mg daily for 6 months, or oral metformin 850mg twice a day and simvastatin 20mg daily also demonstrated clinical efficacy for improvement in acne
The role of metformin in the treatment and prevention of psoriasis has been studied in three RCTs and one retrospective cohort study (n=73,550). Patients were treated with 1,000 to 1,700mg/day oral metformin. All studies demonstrated positive results in both genders and throughout all age groups.
Singh et al conducted two randomized, open-label, placebocontrolled, single-center trials involving treatment of psoriasis with metformin. The initial study evaluated the efficacy and safety of insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome, outcomes for which were evaluated by psoriasis area and severity index (PASI, 0-72) and erythema, scaling, and induration (ESI, 0-9) scores. The primary endpoints were changes in PASI, ESI, and physician global assessment (PGA) scores from baseline after 12 weeks of therapy as compared to placebo. Secondary endpoints included the proportion of patients achieving 75% decrease in PASI and ESI scores in each group. The metformin group had significant improvement in PASI (P=0.001), ESI (P=0.016), and PGA (P=0.012) scores. It should be noted that both metformin and pioglitazone treatment groups had a statistically significant proportion of patients achieving 75% decrease in PASI (P=0.001, P=0.001) and ESI (P=0.001, P=0.001) without any adverse events.5
Singh et al’s more recent study (n=35) investigated the efficacy and safety of metformin in psoriasis patients with metabolic syndrome. Significant improvement in mean percent change of ESI score was observed in the metformin group (P=0.048), whereas no significant percent change was observed in PASI (P=0.215) or PGA scores (P=0.070). There was no statistically significant difference in adverse events between groups with the exception of >1kg weight gain in the placebo group (P=0.042).6
A randomized single-blind clinical trial (n=58) investigated efficacy and safety of metformin as an adjunct to methotrexate for treatment psoriatic arthritis (PsA). A significantly higher percentage (41%; n=12 of 29) of the metformin group achieved an 20% improvement in tender and swollen joints (ACR20) at 24 weeks compared to the placebo group (21%; n=6 of 29; (P<0.001), with greater improvement in Health Assessment Questionnaire- Disability Index (HAQ-DI) (P<0.005), higher PASI75 (P<0.001), and improvements in psoriatic arthritis response criteria (PsARC) score (P<0.001) at week 24 compared to placebo. There was no significant difference in adverse events between groups.7
A case-control study (n=73,404) using the United Kingdom General Practice Research Database (GPRD) to identify patients with a first-time diagnosis of psoriasis and identical number of control subjects, demonstrated that patients who received ≥15 prescriptions of metformin had reduced psoriasis risk (OR 0.77, 95% CI 0.62–0.96).8
Acanthosis Nigricans (AN)
The utility of metformin to treat AN in both male and female patients (n=57), age range, 12–45 years old, has been reported in five case reports, one RCT, two prospective cohorts, one retrospective cohort, and one case series. Various doses have been studied in adult patients ranging from 500 to 2000mg daily, as well as weight-based dosing at 25mg/kg/day.9 Metformin was noted to be an efficacious treatment for AN in 72.2% of patients. Oral metformin was also effective in AN in conjunction with isotretinoin titrated to 40–80mg/day for 2 years, 1.01 units/kg recombinant human insulin-life growth factor (rhIGF1) injections for 5 years, or a carbohydrate-controlled diet for 3 months.9-11 When compared to other diabetes medications, such as rosiglitazone, patients on metformin had greater improvement in skin texture with minimal clinical response.12
Acne
The utility of metformin as a treatment for acne has been described in 11 RCTs and 9 cohort studies. Women with a history of PCOS with acne, and one study involving men with refractory acne, (total n=1,587 patients) were treated with oral metformin (dose range, 1,000–2,550mg/day). All except three studies13-15 reported significant improvement in acne in female patients with PCOS. Only Fabbrocini et al’s study assessed the effects of metformin and a low glycemic diet on male subjects with resistant acne.16 While the study led to statistically significant improvement in acne in the experimental group receiving metformin and undergoing low glycemic diet (P<0.05), the low sample size (n=20) and lack of stratification necessitates followup studies. Metformin was generally well tolerated with the exception of gastrointestinal intolerance (nausea, vomiting, diarrhea, loss of appetite), with only few patients discontinued the studies.17,18 Although dosage correlation studies were not performed, both obese and lean patients (31.8 vs 11.6%; all P<0.017) with insulin resistance benefited from their metformin treatments over a 6-month period with dose adjustment ranging from 500–1000mg.19,20
No improvement was noted in three studies.18,21,22,23,24 Adding metformin did not lead to significant improvement in acne patients with clinical manifestations of hyperandrogenism and elevated DHEAS experienced a significant decrease in acne score by 14% (P<0.0005).21 Adding metformin to estrogen and anti-androgen medications (ie, cyproterone acetate or EE-CA) failed to significantly improve acne (P=0.79), suggesting a lack of pharmacological synergy.18,22,23,24 Both Navali et al’ and Fruzzetti et al’s studies demonstrated that statins (20mg/day simvastatin and 4 g/day myo-inositol, respectively) are superior to 1.5g/ day metformin for treating acne (P<0.05) among other PCOS parameters.15,25 Combination therapy of metformin 850mg with pioglitazone 7.5mg daily, flutamide 62.5mg daily for 6 months, or oral metformin 850mg twice a day and simvastatin 20mg daily also demonstrated clinical efficacy for improvement in acne
