Study summary · research use only
[Obesity: a review of currently used antiobesity drugs and new compounds in clinical development]
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review summarizes currently used antiobesity drugs and compounds in clinical development (human context). It reports three drugs accepted for long-term use: sibutramine, a noradrenaline and serotonin reuptake inhibitor said to reduce body weight by about 4-5 kg but to increase heart rate and blood pressure; orlistat, a gastrointestinal lipase inhibitor associated with about 3 kg mean weight loss and reduced incidence of type 2 diabetes in impaired glucose tolerance, with gastrointestinal adverse effects; and rimonabant, a CB1 receptor antagonist associated with 4-5 kg mean weight loss but anxiety and depressive disorders. The authors note absent chronic-administration data and describe new compounds under development, including agents acting on central neurotransmitters, neuropeptides (leptin analogues, NPY antagonists), satiety signals (PYY3-36), thermogenic agents, and others such as AOD9604 and cetilistat.
Abstract
This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).
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