Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort)

Abstract

Background: Increased prevalence of metabolic syndrome (MS) is observed in psoriasis. Metformin has shown improvement in cardiovascular risk factors while pioglitazone demonstrated anti proliferative, anti-inflammatory and anti angiogenic effects. Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS).

Methods: Single centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS.

Results: Statistically significant improvement was observed in Psoriasis Area and Severity Index (PASI), Erythema, Scaling and Induration (ESI) and Physician global assessment (PGA) scores in pioglitazone (p values - PASI = 0.001, ESI = 0.002, PGA = 0.008) and metformin groups (p values - PASI = 0.001, ESI = 0.016, PGA = 0.012) as compared to placebo. There was statistically significant difference in percentage of patients achieving 75 % reduction in PASI and ESI scores in metformin (p value - PASI = 0.001, ESI = 0.001) and pioglitazone groups (p vaue - PASI = 0.001, ESI = 0.001). Significant improvement was observed in fasting plasma glucose (FPG) and triglycerides levels in metformin and pioglitazone arms. Significant improvement was noted in weight, BMI, waist circumference, FPG, triglycerides and total cholesterol after 12 weeks of treatment with metformin while pioglitazone showed improvement in FPG, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and LDL cholesterol levels. There was no difference in pattern of adverse drug reaction in three groups.

Conclusion: Insulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients.

Trial registration: CTRI Registration Number: CTRI/2011/12/002252 . Registered on 19/12/2011.

Keywords: Insulin sensitizers; Metabolic syndrome; Metformin; Pioglitazone; Psoriasis.

Fig. 1

Flowchart of the patients enrolled in the study depicting enrollment, withdrawal and follow up of the subjects

Fig. 2

Mean change in PASI, ESI and PGA scores in three treatment groups from baseline (Intention to treat Analysis). || = Inter-group comparisons for PASI, ESI and PGA scores at 12 weeks as compared to baseline was carried out by One Way ANOVA, post hoc test used Scheffe; † = metformin vs placebo, ‡ = Pioglitazone vs placebo,** = metformin vs pioglitazone. PASI - Psoriasis area and severity index, ESI – Erythema, Scaling and Induration, PGA – Physician Global Assessmenty

Fig. 3

Percentage of parameters of metabolic syndrome (MS) improved following 12 weeks of treatment in placebo, metformin and pioglitazone groups from baseline (Intention to treat Analysis). Inter-group comparisons for percentage of parameters of metabolic syndrome improved carried out by Chi-square test. * = Placebo vs metformin, † = placebo vs pioglitazone, ‡ = metformin vs pioglitazone; MS = Metabolic syndrome

Fig. 4

Percentage of patients achieving 75 % reduction in PASI, ESI and PGA scores in placebo, metformin and pioglitazone groups from baseline (Intention to treat Analysis). Inter-group comparisons for 75 % reduction in PASI, ESI and PGA scores between three treatment groups carried out by Chi-square test. * = placebo vs metformin, † = metformin vs pioglitazone, ‡ = placebo vs pioglitazone. PASI - Psoriasis area and severity index, ESI – Erythema, Scaling and Induration, PGA – Physician Global Assessment

Fig. 5

Mean decrease in levels of IL-6 and TNF-α in three treatment groups from baseline in subgroup of patients (Intention to treat Analysis). Values are expressed as Mean ± SD. Inter-group comparisons for IL-6 and TNF-α carried out by One way ANOVA, *- Metformin vs placebo, †- pioglitazone vs placebo, ‡ - metformin vs pioglitazone, IL-6 – Interleukin-6, TNF-α – Tumor necrosis factor-α