Phentermine plus topiramate in the treatment of obesity

The Lancet (Impact Factor: 45.22). 07/2011; 378(9786):125-6; author reply 126-7. DOI: 10.1016/S0140-6736(11)61080-5
Source: PubMed
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    • "This distinguishes ER-b–selective ligands from most of the new chemical entities under development [e.g., Lorcarserin (Arena Pharmaceuticals), Qnexa (Vivus Inc.), and Contrave (Orexigen Ltd.)], which reduce body weight by suppressing appetite through targets in the central nervous system. Unfortunately, many anti-obesity drugs belonging to similar classes were eventually withdrawn from the market due to cardiovascular side effects (Connolly et al., 1997; Malgarini and Pimpinella, 2011). Since long-term activation of ER-a could have unwarranted side effects (e.g., thromboembolism and breast and uterine cancers), we examined the effects of ER-b–selective agonists on the hypothalamus– pituitary–gonadal axis in males fed a high-fat diet and on uterine weight in females with ovariectomy-induced weight gain to ensure the absence of cross-reactivity with ER-a. "
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    ABSTRACT: Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.
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