Review Paper: Current Strategies in the Development of Anti-obesity Drugs and Their Safety Concerns

Abstract

Obesity is a well-established risk factor for hypertension, hyperlipidemia, type II diabetes, coronary heart disease, stroke, obstructive sleep apnea, asthma, orthopedic disorders, and certain cancers. Despite this risk, the prevalence of obesity continues to increase worldwide, and there is a growing demand for safe and effective antiobesity drugs. Previous antiobesity drugs or anorexigens, particularly centrally acting agents, have poor safety records. Life-threatening safety issues led to the withdrawal of aminorex in 1968, fenfluramine and dexfenfluramine in 1997, and phenylpropanolamine in 2000. Many of the safety issues, such as valvulopathy with fenfluramine and pulmonary arterial hypertension with aminorex, were initially not predicted by routine preclinical toxicology studies. To date, there are no validated animal models or preclinical and/or toxicologic screens to accurately predict anorexigen-induced valvulopathy and pulmonary arterial hypertension in humans. This review covers the current state of antiobesity drugs and their safety concerns, and highlights new therapeutic targets and scientific advances toward the development of appropriate animal models by using novel techniques that will aid in understanding pathogenesis and pathophysiology of anorexigen-related safety issues.

Overview of bariatric surgery for the physician

“…Anaemia can also be caused by deficiencies in folate, vitamin B 12 , vitamin E (haemolytic anaemia), copper (anaemia and neutropenia), vitamin A and zinc. In refractory anaemia, gastrointestinal blood loss must be considered.…”

“…1 Diet, exercise and drug treatments for severe obesity have been disappointing. [1][2][3][5][6][7][8][9][10][11][12] At the present time, bariatric surgery is the only treatment that reliably produces substantial and sustainable weight loss. [1][2][3][4][5][6][7]9,13 It is indicated in people with BMI >40 kg/m 2 or with BMI >35 kg/m 2 in the presence of significant comorbidity.…”

Erratum: Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects

“…26,55,56 GSK1521498 was generally well tolerated compared with placebo, with no deleterious effects detected on anxiety, mood or other aspects of hedonic function or on liver or other blood safety parameters. Akin to previous studies, 31,32 transient impairments on subjective ratings of alertness, contentedness and calmness, were seen with GSK1521498 on the first day of active treatment, largely driven by relative increases in the placebo group.…”

Enzyme-treated Ecklonia cava extract inhibits adipogenesis through the downregulation of C/EBPα in 3T3-L1 adipocytes

“…A number of these drugs have been withdrawn from the market because of low efficacy and side effects, thus only a few drugs remain (27,28). For example, the anti-obesity drugs orlistat (Xenical ® ) and sibutramine are commonly prescribed, although they are associated with significant side effects such as bladder pain, diarrhea, fever, loss of appetite, nasal congestion and difficulty in sleeping (orlistat), and headache, insomnia, increased appetite, asthenia, nausea and anorexia (sibutramine) (29–31).…”