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

Abstract

BackgroundIncreased 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).MethodsSingle centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS.ResultsStatistically 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.ConclusionInsulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients.Trial registrationCTRI Registration Number: CTRI/2011/12/002252. Registered on 19/12/2011.

A unified mitochondria mechanistic target of rapamycin acyl‐coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells

“…Recent work suggests that metformin, as a biguanide agent, directly as well as indirectly improved insulin sensitivity and consequently decreased hyper‐insulinemia, and had a lower occurrence of psoriasis than other insulin‐sensitizing agents among patients with diabetes . Metformin has shown improvement in psoriasis and parameters of psoriasis patients having metabolic syndrome . Moreover, long‐term treatment with metformin was closely linked to a reduced risk of psoriasis based on a large case‐control study .…”

Effects of combination of mitiglinide with various oral antidiabetic drugs in streptozotocin‐nicotinamide‐induced type 2 diabetic rats and Zucker fatty rats

“…In diabetes treatment, insulin sensitizers are used for patients with strong insulin resistance or who are overweight or obese. α‐GIs are used for patients with insulin‐independent postprandial hyperglycaemia who do not exhibit very high fasting blood glucose levels . Furthermore, SGLT2 inhibitors that also inhibit SGLT1 have been recently used .…”

Glycemic Control in the Treatment of Psoriasis

“…A double-blinded randomized controlled trial of pioglitazone discovered a significant dose-dependent reduction in PASI within 2 weeks of treatment without adverse effects [55] . Another recent open-label randomized controlled trial demonstrated that treatment with pioglitazone significantly improved psoriasis in patients with a concomitant metabolic disorder [56] . Furthermore, patients with psoriatic arthritis showed improvement in psoriatic plaques and joint pain with pioglitazone therapy [57] .…”

“…However, given the increasing evidence of an association between psoriasis and insulin resistance [71] , it remains to be determined whether insulin sensitization by thiazolidinediones contributes to the relief of psoriasis. One clinical trial in patients with both metabolic disorder and psoriasis demonstrated simultaneous improvements in psoriasis and glucose levels, among other metabolic parameters [56] .…”

“…A populationbased study also demonstrated that frequent usage of metformin reduced the incidence of new-onset psoriasis in patients with diabetes [4] . A single open-label randomized controlled trial demonstrated statistically significant improvement of psoriasis with metformin treatment in comparison to placebo in patients with a concomitant metabolic disorder [56] .…”