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Obesity
Published in Geoffrey P. Webb, Nutrition, 2019
Up until 1997, fenfluramine and dexfenfluramine were the most widely used anti-obesity drugs in the UK and Europe. They act to increase the activity of the nerve transmitter serotonin or 5HT (5-hydroxytryptamine) in the brain. They block the re-uptake of serotonin which is the normal mechanism for inactivation of this transmitter after its release. When serotonin (5HT) is injected into the brains of animals, it also decreases feeding. These drugs mimic the actions of serotonin but do not have the addictive dopamine-like effects of the amphetamines. They act not by reducing the desire to eat but by causing the patient to feel full or satiated earlier. Fenfluramine was in use for about 30 years and tens of millions of Europeans took these drugs over that period (over 60,000 Britons in 1996 alone). In 1996, they were finally approved by the FDA for use in the USA. Long-term studies of over a year have reported significantly greater weight loss in people treated with drug and diet as compared to diet and placebo. Rare but potentially fatal side effects of these drugs had been known for some time (pulmonary hypertension), and there were suggestions from animal experiments that they may damage serotonin-producing brain cells. However, in 1997 new evidence was produced in the USA suggesting that they might cause damage to heart valves. This led to both drugs being withdrawn from the market in both Europe and the USA.
Future Directions in Obesity and Weight Management
Published in James M. Rippe, Lifestyle Medicine, 2019
Prior to 2013, very little innovation in pharmacotherapy could be found. The FDA approved phentermine for weight loss in 1959. The first significant new drug approval after that came in 1996 with dexfenfluramine. In 1997, it was withdrawn from the market after reports of an unacceptable risk of valvular heart disease.41 The FDA approved two other prescription drugs, sibutramine and orlistat, shortly after dexfenfluramine. Both of those drugs were marketed more for weight loss than for chronic disease management of obesity, and both had disappointing results in market. Sibutramine was withdrawn in 2010.42
Obesity and diet
Published in Clive Handler, Gerry Coghlan, Marie-Anne Essam, Preventing Cardiovascular Disease in Primary Care, 2018
Clive Handler, Gerry Coghlan, Marie-Anne Essam
Dexfenfluramine, fenfluramine and amphetamines should no longer be prescribed for obesity. They cause pulmonary hypertension and valvular heart disease. There is no evidence that methylcellulose is effective or safe. Phentermine is a catecholamine-releasing agent stimulating the central nervous system causing appetite suppression. It should not be prescribed because its efficacy and safety have not been established.
The safety of pharmacologic treatment for pediatric obesity
Published in Expert Opinion on Drug Safety, 2018
Ariana M. Chao, Thomas A. Wadden, Robert I. Berkowitz
Several medications tested in pediatric and adult samples have been withdrawn from the market due to serious adverse events. For example, sibutramine, a serotonin and norepinephrine reuptake inhibitor, was effective when combined with a family-based lifestyle program in inducing and maintaining weight loss in adolescents with obesity [10,11]. The medication also was associated with improved cardiometabolic risk factors. However, the drug was withdrawn from the market in 2010 because of findings that it increased the risk of non-fatal myocardial infarction and nonfatal stroke in adults with a history of cardiovascular disease [12]. Other medications, such as fenfluramine, benfluorex, dexfenfluramine, and rimonabant have also been withdrawn due to concerns about cardiovascular and psychiatric effects [13–17]. Thus, there is heightened concern about the potential toxicity of weight loss medications.
The limits and challenges of antiobesity pharmacotherapy
Published in Expert Opinion on Pharmacotherapy, 2020
Kishore M Gadde, Katelyn D Atkins
In 1995, the FDA held an advisory committee meeting which led to the recognition that obesity is a chronic disease and hence short-term treatment would not confer long-term benefits [12]. This view was reflected in the first FDA guidance document for development of antiobesity drugs in 1996, which required demonstration of weight loss efficacy over a minimum duration of 1 year [13]. In 1996, dexfenfluramine became the first antiobesity drug approved for long-term use. Just over a year later, it was removed from the market, along with fenfluramine which was available since 1973, after data emerged that linked the use of these two drugs with cardiac valvulopathy [14].
An evaluation of liraglutide including its efficacy and safety for the treatment of obesity
Published in Expert Opinion on Pharmacotherapy, 2020
Chen-Hsiu Lin, Li Shao, Yu-Mei Zhang, Yu-Ju Tu, Yuzhen Zhang, Brian Tomlinson, Paul Chan, Zhongmin Liu
The amphetamines, dexamphetamine and methamphetamine, were withdrawn because of problems of dependency and abuse potential. Fenfluramine and dexfenfluramine were withdrawn because of the association with heart valve abnormalities and pulmonary hypertension. Sibutramine looked promising but was withdrawn because it was found to be associated with an increase in blood pressure, heart rate and cardiovascular events, presumably through a sympathomimetic effect [14]. Rimonabant, a central cannabinoid type-1 receptor inhibitor, was effective in weight reduction but was withdrawn as it was found to be associated with increased anxiety, depression and suicidal ideation.