Modest weight loss if maintained is associated with significant metabolic benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines believed to contribute to the pathogenesis of insulin resistance and cardiovascular risk. We therefore observed the effect of modest weight loss on serum adipocytokines and their relationship with changes in anthropometric and metabolic parameters within a period of 6 months in the setting of a routine obesity hospital clinic after various medical treatments. In this prospective, nonrandomized, nonblinded observational study, patients were first given treatment (sibutramine or orlistat) as decided by the treating clinician and then allocated into 1 of 2 groups according to the treatment prescribed. The first group included 21 Caucasian nondiabetic female subjects, with a mean (+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss. The second group included 20 Caucasian nondiabetic female subjects, mean age 42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1 month on a low-fat (</=30%) diet in this group. Blood pressure and anthropometric measurements were performed before and after weight loss by a single observer. Serum glucose, insulin, lipid profile, C-reactive protein (CRP), resistin, leptin, and adiponectin were measured before and after weight loss on a fasting sample. After 6 months, the sibutramine group had a modest mean weight loss of 5.4% (P =.0001), and waist circumference was reduced by 4.5 +/- 1.4 cm. There was a decrease in serum resistin, leptin, and CRP levels, and a rise in serum adiponectin (P <.05). Change (%) (Delta) in BMI (DeltaBMI%) was associated with Deltainsulin(%) (P =.02, r = 0.53) and Deltaleptin(%) (P =.01, r = 0.58). Change in waist was associated with Deltainsulin(%) (P =.005, r = 0.75) and Deltaresistin(%) (P =.03, r = -0.55). The orlistat-treated group had a mean weight loss of 2.5%. Although this group did not show significant change in metabolic parameters, surprisingly there was a greater decrease of resistin (P =.02) associated with comparable (%) increase in adiponectin and (%) reduction of waist circumference and CRP. We conclude that modest weight loss (>5%) after medical treatment in a routine obesity hospital clinic is associated with improvements in insulin sensitivity and lipid profile. Modest weight loss is also associated with potentially favourably changes in serum adipocytokines, particularly in a rise of serum adiponectin. Reduction of waist circumference is associated with a change in serum resistin.