Sibutramine: current status as an anti-obesity drug and its future perspectives

Sharma, Bikash; Henderson, David C.

doi:10.1517/14656566.9.12.2161

Cited by 24 publications

(11 citation statements)

References 149 publications

(148 reference statements)

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“…The pharmacological treatment of DIO rodents with anti-obesity agents, such as sibutramine and liraglutide, has been shown to have effects comparable to those reported in humans. Sibutramine reduces food intake, but there are conflicting data as to whether sibutramine has an effect on energy expenditure [67] . In DIO rats, sibutramine has also been shown to reduce body weight compared to placebo (9%) because of a reduction in food intake.…”

Section: Polygenic Modelsmentioning

confidence: 99%

Laboratory animals as surrogate models of human obesity

Nilsson¹,

Raun²,

Yan³

et al. 2012

Acta Pharmacol Sin

239

104

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Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world. Great emphasis has been put on establishing treatments for this condition, including pharmacological intervention. However, there are many obstacles and pitfalls in the development process from pre-clinical research to the pharmacy counter, and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health. Hence, it is important to test potential new drugs in a valid translational model early in their development. In the current mini-review, a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character.Keywords: obesity; animal models; sibutramine; liraglutide; KK-A y mice; ob/ob mice; Zucker rat; diet-induced obesity models Acta Pharmacologica Sinica (2012) 33: 173-181; doi: 10.1038/aps.2011 Review IntroductionAs the prevalence of obesity is rising along with its socioeconomic consequences, the quest to find new treatments or a cure is also increasing (http://www.who.int/mediacentre/ factsheets/fs311/en/). Pharmaceutical treatment is one avenue that has been pursued, but currently there are only a limited number of compounds on the market because many have failed or been withdrawn because of side effects. Given that the development process from initial idea to marketed product typically requires more than 10 years and the attrition rate is notably high, it is important that the models used, whether in vitro or in vivo, are good surrogates for human obesity. Depending on the target in question, there are a number of models that can be applied. In the following pages, we will review the most widely used animal models in obesity research. We have categorized the different models into groups; rodent models are divided into monogenetic, polygenetic, and selectively bred diet-induced obesity (DIO) models, and finally we discuss the DIO pig model. To demonstrate the translational potential of the selected models, we have chosen two different model compound families that have been tested in human cohorts -sibutramine and liraglutide or other glucagon-like peptide-1 (GLP)-1 analogues [1 , 2] . Sibutramine is a serotonin and norepinephrine re-uptake inhibitor that was developed for the treatment of obesity and has been on the market for the past 9 years, although in most markets it has been withdrawn because of undesirable side effects [3] . Liraglutide is a GLP-1 analogue currently in phase 3 clinical development for severe obesity after demonstrating positive results in phase 2 trials [2] . By choosing the best suited animal model for a particular study, it is possible to make a qualified assessment as to whether target X and/or compound Y will have an impact in clinical practice at a much earlier point. Monogenic modelsKK-A y mice The inbred mouse strain KK was established in Japan and is a mouse model with peripheral insulin sensitivity and glucose intolerance [4] . Insulin resistance in the KK mouse i...

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Section: Polygenic Modelsmentioning

confidence: 99%

Laboratory animals as surrogate models of human obesity

Nilsson¹,

Raun²,

Yan³

et al. 2012

Acta Pharmacol Sin

239

104

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“…[25][26][27][28] Sibutramine is one of the few established and well-proven agents for obesity and may be considered effective in the management of patients requiring pharmacotherapy as part of the multi-modal approach to weight-loss. [29][30][31][32] Though this serotonin-norepinephrine reuptake inhibitor was originally evaluated for possible use as an antidepressant, its research development was redirected to evaluate it as an anorexiant. [33] The pharmacological mechanisms by which sibutramine exerts its weight loss effect are likely due to a combination of reduced appetite, feelings of satiety, and possibly the induction of thermogenesis.…”

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confidence: 99%

Cardiovascular Risk-Benefit Profile of Sibutramine

Scheen

2010

American Journal Cardiovascular Drugs

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SUMMARYSibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to what was previously reported with some other anti-obesity agents. However, it exerts

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“…12,13 In the present paper we describe the mechanism of action of sibutramine and present the most important trials that evaluated the body weight-reduction potential of this agent. Furthermore, we comment on recent studies evaluating the effects of sibutramine on cardiometabolic risk factors and in specific pathological conditions related with obesity such as polycystic ovary syndrome, sleep apnea syndrome, left ventricular hypertrophy, binge eating disorder and in adolescent obesity.…”

Section: Dovepressmentioning

confidence: 99%

“…30 In addition, it should not be administered to patients receiving monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, sumatriptan, dihydroergotamine, meperidine, methadone, pentazocine, fentanyl, lithium or tryptophan. 13,30 However, a Swedish study reported that 28% of the patients prescribed sibutramine had one or more contraindications to its use. 47 In the larger sibutramine studies, discontinuation rates at one and two years of treatment were 19%-49% and 42%, respectively.…”

Section: Safety Considerationsmentioning

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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Sibutramine: current status as an anti-obesity drug and its future perspectives

Cited by 24 publications

References 149 publications

Laboratory animals as surrogate models of human obesity

Laboratory animals as surrogate models of human obesity

Cardiovascular Risk-Benefit Profile of Sibutramine

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

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