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 Unfortunately, many anti-obesity drugs belonging to similar classes were eventually withdrawn from the market due to cardiovascular side effects (Connolly et al., 1997; Malgarini and Pimpinella, 2011).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: This article is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 12 meeting in San Diego, CA. The presentations discussed the roles of a number of nuclear receptors in regulating glucose and lipid homeostasis, the pathophysiology of obesity-related disease states and the promise associated with targeting their activities to treat these diseases. While many of these receptors, in particular constitutive androstane receptor and pregnane X receptor and their target enzymes have been thought of as regulators of drug and xenobiotic metabolism, this symposium highlighted the advances made in our understanding of the endogenous functions of these receptors. Similarly, the advances made in our understanding of the mechanisms underlying bile acid signaling pathways in the regulation of body weight and glucose homeostasis illustrates the importance of using complementary approaches to elucidate this fascinating network of pathways. The observations that some receptors, like the farnesoid X receptor can function in a tissue specific manner via well defined mechanisms has important clinical implications particularly in the treatment of liver diseases. Finally, the novel findings that agents that selectively activate estrogen receptor β can effectively inhibit weight gain in a high-fat diet model of obesity identifies a new role for this member of the steroid superfamily. Taken together, this symposium has revealed a number of significant findings that illustrate the promise associated with targeting a number of nuclear receptors for the development of new therapies to treat obesity and other metabolic disorders.
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    ABSTRACT: Long-term pharmacologic strategies that may be used in conjunction with lifestyle changes to combat the obesity epidemic have, until recently, been an unmet clinical need. In 2012, the US Food and Drug Administration (FDA) approved two new drugs for chronic weight management in obese adults in conjunction with a reduced-calorie diet and increased physical activity: phentermine/topiramate extended-release (PHEN/TPM ER) and lorcaserin. The efficacy and safety of PHEN/TPM ER has been studied in clinical trials. PHEN/TPM ER had a substantial impact on weight loss with the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) target of 10 % weight loss from baseline being achieved in almost half of patients receiving PHEN/TPM ER 15/92. Furthermore, PHEN/TPM ER was associated with improvement in obesityrelated adverse health consequences, including hyperglycemia, dyslipidemia, and hypertension, and a reduction in the rate of progression to type 2 diabetes. This clinical evidence supports PHEN/TPM ER as an efficacious, well-tolerated anti-obesity agent that may also have a significant impact on obesity-related adverse health consequences.
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