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The relationship between weight reduction after sibutramine treatment and a single nucleotide polymorphism, rs5443 (C825T), in the guanine nucleotide binding protein β polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 single nucleotide polymorphism could influence weight reduction and body composition change under sibutramine therapy in 131 obese Taiwanese patients. By comparing the sibutramine and placebo groups with analysis of covariance, our data showed a strong effect of sibutramine on weight reduction (7.4±1.4 vs. 3.4±1.2 kg; P<0.001) and on body fat percentage loss (4.2±0.1 vs. 2.1±0.1%; P<0.001) in the combined TT+TC carriers. In contrast, sibutramine caused no significant additional effect on weight loss (P = 0.078) or on body fat percentage loss (P = 0.441) in homozygous C allele carriers.