A Controlled Pharmacogenetic Trial of Sibutramine on Weight Loss and Body Composition in Obese or Overweight Adults

Grudell, April; Sweetser, Seth; Camilleri, Michael; Eckert, Deborah J.; Vázquez-Roque, María I.; Carlson, Paula; Burton, Duane D.; Braddock, Autumn E.; Clark, Matthew M.; Graszer, Karen M.; Kalsy, Sarah A.; Zinsmeister, Alan R.

doi:10.1053/j.gastro.2008.07.009

Cited by 42 publications

(39 citation statements)

References 45 publications

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“…In addition, previous studies (Grudell et al 2008;Hauner et al 2003;Hsiao et al 2009) in pharmacogenetics suggested that the GNB3 rs5443 SNP could influence weight reduction and body composition change under sibutramine therapy. The observation of Grudell et al (2008) and Hsiao et al (2009) in their studies showed that the GNB3 TT/TC genotypes were associated with greater weight loss with the sibutramine group than with the placebo group.…”

Section: Discussionmentioning

confidence: 96%

“…The observation of Grudell et al (2008) and Hsiao et al (2009) in their studies showed that the GNB3 TT/TC genotypes were associated with greater weight loss with the sibutramine group than with the placebo group. In contrast to Grudell et al (2008) and Hsiao et al's (2009) studies, a report by Hauner et al (2003) indicated that individuals with the GNB3 CC genotype were associated with more weight loss from sibutramine administration. In addition, Grudell et al's (2008) analyses were consistent with Hsiao et al's (2009) results that treatment with sibutramine resulted in significantly greater reduction in body fat for specific GNB3 TC/TT genotypes.…”

Section: Discussionmentioning

confidence: 98%

“…Odds ratios (ORs) and their 95 % confidence intervals (CIs) were evaluated. As the method adopted in this study was similar to the previous studies (Grudell et al 2008;Hauner et al 2003;Hsiao et al 2009) of investigating the GNB3 rs5443 polymorphism, we performed odds ratio analysis by comparing CC genotypes with the combined CT and TT genotypes. The criterion for significance was set at P \ 0.05 for all tests.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, data from a study support the notion that there was statistically significant association of this SNP with total cholesterol levels in a Japanese population (indicating higher in subjects with the T allele) (Ishikawa et al 2000), even though there are some conflicting results in another Japanese study showing no association with cholesterol (Suwazono et al 2006). Moreover, previous pharmacogenetic studies (Grudell et al 2008;Hauner et al 2003;Hsiao et al 2009) have revealed that the GNB3 rs5443 polymorphism was associated with weight reduction with sibutramine treatment in overweight or obese participants, suggesting either the T allele (Grudell et al 2008;Hsiao et al 2009) or the C allele (Hauner et al 2003) with greater weight loss.…”

Section: Introductionmentioning

confidence: 95%

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Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

et al. 2012

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The relationship between obesity and a single nucleotide polymorphism (SNP), rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 SNP could influence obesity and obesity-related metabolic traits in a Taiwanese population. A total of 983 Taiwanese subjects with general health examinations were genotyped. Based on the criteria defined by the Department of Health in Taiwan, the terms ''overweight'' and ''obesity'' are defined as 24 2 BMI \ 27 and BMI 3 27, respectively. Compared to the carrier of the combined CT ? TT genotypes of the GNB3 rs5443 polymorphism, triglyceride was significantly higher for the carrier of CC genotype in the complete sample population (128.2 ± 93.2 vs. 114.3 ± 79.1 mg/dl; P = 0.041). In addition, the carriers of CC variant had a higher total cholesterol than those with the combined CT ? TT variants (194.5 ± 36.8 vs. 187.9 ± 33.0 mg/dl; P = 0.019) in the complete sample population. In the normal controls, both triglyceride (P = 0.018) and total cholesterol (P = 0.011) were also significantly higher in the CC homozygotes than in the combined CT ? TT genotypes. However, the GNB3 rs5443 SNP did not exhibit any significant association with obesity or overweight among the subjects. Our study indicates that the CC genotype of the GNB3 rs5443 SNP may predict higher obesity-related metabolic traits such as triglyceride and total cholesterol in non-obese Taiwanese subjects (but not in obese subjects).

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

et al. 2012

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“…19,49,50 Preliminary findings suggest that specific genes might modulate the response to sibutramine treatment. [51][52][53] In 149 obese women, the GG and AA genotypes of the phenylethanolamine N-methyltransferase gene (the ratelimiting enzyme in catecholamine biosynthesis) were associated with greater weight loss with sibutramine than the AG genotype. 51 Another study in 111 patients reported that the GNβ3 CC genotype predicted 5% weight loss with sibutramine.…”

Section: Studies Assessing the Weight-lowering Potential Of Sibutraminementioning

confidence: 99%

The use of sibutramine in the management of obesity and related disorders: An update

Tzotzas¹,

Krassas²,

Τζιόμαλος³

et al. 2009

VHRM

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Aims:To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders. Methods and results:The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesityassociated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. Conclusions: Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality.

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Exploratory Literature Meta‐Analysis to Characterize the Relationship Between Early and Longer Term Body Weight Loss for Antiobesity Compounds

Plock

Bax

Lee

et al. 2016

The Journal of Clinical Pharma

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The presented analysis was performed to characterize the relationship between treatment-related early (week 4) and longer term (3-6 months) weight loss to understand the potential utility of 4-week proof-of-mechanism studies in the early decision-making process during clinical development of new antiobesity compounds. A regression-based meta-analysis was performed leveraging publically available clinical outcomes data to (1) characterize the within-trial relationship between treatment-related early and longer term body weight loss and (2) identify and quantify key covariate effects on this relationship. Data from 89 randomized clinical trials with 209 treatment arms, representing observations from 54 461 patients and 9 treatments, were available for the meta-analysis. Results indicated that (1) there is a correlation between treatment-related early and longer term body weight loss (r > 0.9), (2) baseline body weight influences the relationship between early and longer term weight loss, whereas comorbidity such as type 2 diabetes mellitus, class of drugs including GLP-1 analogues and the antiobesity compounds lorcaserin or phentermine/topiramate showed no significant effects on this relationship. The model was externally evaluated with data from the investigational compound beloranib, for which longer term weight loss could be successfully predicted based on early response data. Based on these results, the identified strong relationship between treatment-related early and longer term weight loss appears to be independent of mechanism of action. Thus, findings from this analysis can optimize design of clinical studies and facilitate development of new anti-obesity compounds.

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A Controlled Pharmacogenetic Trial of Sibutramine on Weight Loss and Body Composition in Obese or Overweight Adults

Abstract: Background/ Aim-Weight loss in response to sibutramine is highly variable. We assessed the association of specific markers of polymorphisms of candidate a2A adrenoreceptor, 5-HT transporter and GNβ3 genes and weight loss with sibutramine.

Cited by 42 publications

References 45 publications

Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population

The use of sibutramine in the management of obesity and related disorders: An update

Exploratory Literature Meta‐Analysis to Characterize the Relationship Between Early and Longer Term Body Weight Loss for Antiobesity Compounds

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