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At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
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Drug Safety
Published in: Drug Safety 4/2006

01-04-2006 | Review Article

Safety of Drug Therapies Used for Weight Loss and Treatment of Obesity

Authors: Dr Lisa L. Ioannides-Demos, Joseph Proietto, Andrew M. Tonkin, John J. McNeil

Published in: Drug Safety | Issue 4/2006

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Abstract

Some of the medications used for weight loss in the management of obesity have been associated with unacceptable morbidity and mortality. Safety concerns have led to the withdrawal of aminorex, followed by the fenfluramines in 1997, and phenylpropanolamine (norephedrine) in 2000. Aminorex was associated with an increased prevalence of primary pulmonary hypertension (PPH), fenfluramines with an increased prevalence of PPH and valvulopathy, and phenylpropanolamine with an increased risk of haemorrhagic stroke.
Several studies have investigated the safety of the fenfluramines, yet the benefit-risk profile has not been conclusively quantified. This is due to several deficiencies in the published studies, including a lack of data on the baseline prevalences of comorbid conditions in obese subjects, and potential confounders and biases in the study designs. Although several studies and systematic reviews support an increased risk of PPH and valvulopathy in patients who have taken fenfluramines, without knowledge of the background prevalence it is not possible to determine if the exposure preceded the outcome. The population at higher risk of these adverse effects includes those taking higher doses or with a longer duration of exposure to fenfluramines and those with pre-existing cardiac disease or a genetic predisposition. Patients exposed to fenfluramines continue to be monitored, with some follow-up studies indicating no overall worsening in valvulopathy over time.
There are limited efficacy and safety data for amfepramone (diethylpropion) and phentermine and their approval for the management of obesity is limited to short-term use. Orlistat and sibutramine are the only currently approved medications for long-term management of obesity. Although the benefit-risk profiles of sibutramine and orlistat appear positive, sibutramine continues to be monitored because of long-term safety concerns.
The safety and efficacy of currently approved drug therapies have not been evaluated in children and elderly patient populations and there is limited information in adolescents, whilst the long-term safety of current and potential new drug therapies in adults will require several years of postmarketing surveillance to fully elucidate their adverse effect profiles.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
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Metadata
Title
Safety of Drug Therapies Used for Weight Loss and Treatment of Obesity
Authors
Dr Lisa L. Ioannides-Demos
Joseph Proietto
Andrew M. Tonkin
John J. McNeil
Publication date
01-04-2006
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 4/2006
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200629040-00001

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