Food and Drug Administration's Obesity Drug Guidance Document A Short History

Division of Metabolism and Endocrinology Products, Office of Drug Evaluation II, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Circulation (Impact Factor: 14.95). 05/2012; 125(17):2156-64. DOI: 10.1161/CIRCULATIONAHA.111.028381
Source: PubMed
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    ABSTRACT: Background/Objectives:The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both placebo and sibutramine groups.Subjects/Methods:9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg/m(2) were included in this current sub-analysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of: nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest, or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models.Results:During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 bpm with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12-months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia.Conclusion:Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.International Journal of Obesity accepted article preview online, 18 December 2014. doi:10.1038/ijo.2014.211.
    International journal of obesity (2005) 12/2014; DOI:10.1038/ijo.2014.211 · 5.39 Impact Factor
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    ABSTRACT: Introduction: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. Areas covered: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Expert opinion: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.
    Expert Opinion on Drug Safety 01/2015; 14(2):1-11. DOI:10.1517/14740338.2015.994502 · 2.74 Impact Factor
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    ABSTRACT: The management of obesity remains a major challenge. Dietary therapy often fails, while bariatric surgery although successful, is demanding and applicable to a limited number of patients. Drug therapy has had many setbacks over the past twenty years because of serious adverse effects; however several new drugs for the treatment of obesity are either licensed in some parts of the world, submitted for registration, or completing phase 3 trials. These include combinations (at low dose) of existing drugs e.g. bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide 3mg) and new entities (lorcaserin). Here, we discuss the challenges and opportunities for obesity pharmacotherapy, and review in detail the efficacy of the new drugs in terms of weight loss, and both desirable and potential undesirable cardiovascular and metabolic risk factors. Substantial barriers remain, even if the drugs are approved, in successfully integrating these agents into weight management practice, largely related to cost, patient acceptability and clinician willingness to be engaged in obesity treatment. While hard clinical outcome benefit ( at east for cardiovascular outcomes) has yet to be established obesity pharmacotherapy may soon offer to address many of the challenges in the clinical management of obesity, although newer and better drug combinations, and more evidence of benefit from appropriately designed outcome trials, is needed.
    The Canadian journal of cardiology 11/2014; 31(2). DOI:10.1016/j.cjca.2014.11.010 · 3.94 Impact Factor