Sulfasalazine Improves Insulin Resistance and Endothelial Dysfunction in Metabolic Syndrome Patients

Aim: Metabolic syndrome (MetS) and all its components are independently characterized by the presence of low-grade chronic inflammation. The study aimed at controlling inflammation using sulfasalazine 500mg, once a day treatment in comparison to placebo in MetS patients.

Study Design: Double blind, randomized, placebo controlled study.

Place and Duration of Study: Sadbhavna Medical and Heart Institute, Patiala; and, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, between January-November 2014.

Methodology: 50 eligible subjects (Male / Female = 45/5, n=25/group), fulfilling the National Cholesterol education Program-Adult Treatment Panel (NCEP-ATP III) diagnostic criteria of MetS, were randomly assigned to once daily drug or placebo tablets for 20 weeks. Blood pressure, serum high sensitivity C-reactive protein (hsCRP), tumor necrosis factor–alpha (TNF-α), lipid profile, fasting plasma glucose and insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR), endothelial-dependent flow-mediated dilation (FMD) of brachial artery, right common carotid artery’s intima-media thickness (IMT) and artery stiffness indices [(Young elastic modulus (YEM), stiffness index (SI) and carotid arterial compliance (CAC)] by Doppler Ultrasound were assessed at baseline and after 20 weeks treatment. Tolerability of drug was also measured using hematological and biochemical analysis. Statistical significance was accepted at p ≤.05.

Results: FMD improved as 25.66±6.47% versus 12.41±3.22%, p<0.01; and insulin resistance (HOMA-IR) decreased as 7.05±3.48 versus 11.32±6.08, p<0.01, from baseline in drug group as compared to placebo group, whereas endothelium-independent vasodilatation (p=0.23) and baseline brachial artery diameter (p=0.95) remained unchanged in both the groups. Serum triglycerides (p=0.04), hsCRP (p<0.01) and TNF-α (p<0.01) levels were considerably altered, but there was no effect on carotid IMT, YEM, CAC and SI (all p≥0.05). Biochemical and hematological safety variables were significantly altered, but were still found with-in the normal limits.

Conclusion: Thus, sulfasalazine may prevent cardiovascular disease risk in MetS patients by reducing insulin resistance and endothelial dysfunction via halting inflammatory process. Moreover, it was found tolerable.